SEARCH · PubMed Health

Results for “EXTRACELLULAR FLUID”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources

PubMed1982

Disorders of body fluids, sodium and potassium in chronic renal failure.

A stable volume and composition of extracellular fluid are essential for normal functioning of the body. Since the kidney is primarily responsible for regulating extracellular fluid, loss of kidney function should have catastrophic consequences. Fortunately, even with loss of more than 90 percent of renal function, a remarkable capacity to regulate body fluid volumes and sodium and potassium persists. Nevertheless, this capacity is limited to chronic renal disease and this has important consequences for clinical management of these patients. How can sodium and potassium homeostasis be assessed? Methods for evaluating the steady-state regulation of sodium include measurement of body fluids and their distribution in different compartments and measurement of exchangeable and intracellular sodium. Short-term regulation of body sodium can be assessed from measurement of sodium balance during changes in dietary salt. Potassium is predominantly contained within cells and thus the assessment of its regulation requires special emphasis on measurement of steady-state body stores and potassium distribution across cell membranes. However, the methods used to make all of these measurements require assumptions that may not hold in the altered state of uremia. This raises problems in interpretation requiring critical analysis before conclusions can be made regarding sodium and potassium homeostasis in patients with chronic renal failure. This review focuses on abnormalities of body fluids, sodium and potassium in patients with creatinine clearances of less than 20 ml/min due to chronic renal failure and the impact of conservative therapy, dialysis and renal transplantation on these patients.

Body Fluid Compartments↗

PubMed2003

The mineralization of bone tissue: a forgotten dimension in osteoporosis research.

Osteoporosis treatment should not only prevent the loss of bone tissue, not interfere with apatite and avoid bone mineral changes at the crystal level, but should also increase the mechanical resistance of bone and thus protect the skeleton against new fractures. Mineral substance is crystallized as nonstoichiometric carbonated apatite ionic crystals of small size and extended specific surface. Consequently, they have a very large interface with extracellular fluids, and numerous interactions between ions from the extracellular fluid and ions constituting apatite crystals are thus possible. It is generally agreed that bone strength depends on the bone matrix volume and the microarchitectural distribution of this volume, while the degree of mineralization of bone tissue is almost never mentioned as a determinant of bone strength. We now have evidence that the degree of mineralization of bone tissue strongly influences not only the mechanical resistance of bones but also the bone mineral density. In adult bone, our model is based on the impact of changes in the bone remodeling rate on the degree of mineralization of bone tissue. The purpose of this paper is to report the main results concerning the interactions of strontium (Sr) with bone mineral in animals and in osteoporotic women treated with strontium ranelate (SR). These studies aimed to evaluate using X-ray microanalysis, X-ray diffraction and computerized quantitative contact microradiography: (1) the relative calcium and Sr bone content, (2) the distribution of Sr in compact and cancellous bone, (3) the dose dependence of the deposition of Sr in bone, (4) the interactions between Sr and mineral at the crystal level (in monkeys), (5) the influence of Sr on the mean degree of mineralization of bone tissue and on the distribution of the degree of mineralization of bone tissue, and (6) the bone clearance of Sr over short periods of time (6 and 10 weeks) after cessation of SR administration (monkeys treated for 13 and 52 weeks, respectively). In monkeys killed at the end of exposure (13 or 52 weeks), Sr was taken up in a dose-dependent manner into compact and cancellous bone, with a higher content in new bone than in old bone. The Sr content greatly decreased (about 2-fold) in animals killed 6 or 10 weeks after the end of treatment but this affected new bone almost exclusively. After SR treatment, there were no significant changes in crystal characteristics. Easily exchangeable in bone mineral, Sr was slightly linked to crystals by ionic substitution (generally 1 calcium ion substituted by 1 Sr ion in each unit cell). The degree of bone mineralization was not significantly different in the various groups of monkeys. Thus, at the end of long-term SR treatment and after a period of withdrawal, Sr was taken up in a dose-dependent manner into new bone without alteration of the degree of bone mineralization and with no major modification of bone mineral at the crystal level. In postmenopausal osteoporotic women treated with SR (0.5, 1 and 2 g/day) for 2 years, Sr was dose-dependently deposited into new bone without changes in the degree of mineralization of bone tissue. These findings could reflect dose-dependent stimulation of bone formation and are of potential value for the use of SR in the treatment of osteoporosis. In conclusion, the different studies performed on bone samples from monkeys and humans treated with various doses of SR showed that Sr was heterogeneously distributed between new and old bone but in a dose-dependent manner without alteration of the crystal characteristics and the degree of mineralization of bone tissue, even after long-term administration of often high doses of SR (the highest therapeutic dose used in humans is 4-fold lower than the lowest experimental dose administered to monkeys). This emphasizes the value, as antiosteoporotic treatment, of SR, which is safe at the bone mineral level.

Animals↗

PubMed2002

Sodium regulation during dehydration of a herbivorous and a carnivorous beetle from African dry savannah.

The sodium regulation of carnivorous carabid beetles of the genus Cypholoba and herbivorous tenebrionid beetles of the species Phrynocolus petrosus from dry savannah in East Africa was investigated while the beetles went through dehydration in the laboratory. In both species the water loss took place mainly at the expense of the extracellular fluid, and in both species the loss of extracellular water was accompanied by a loss of extracellular sodium. In the carabid beetles the sodium removed from the extracellular fluid was excreted from the body, while in the tenebrionids sodium was kept within the body. It is proposed that the different manners in which the two species handle their sodium reflect differences in their access to dietary water and sodium.

Journal Article↗

PubMed1975

[Pathogenesis of renal hypertension].

Current pathogenetic concepts regarding renal hypertension are reviewed. Alterations of the renin-angiotensin-aldosterone system (RAA) on the one hand, and disturbances of NaCl and water metabolism on the other, represent the dominant factors in renal hypertension. The present view of the reactions within the RAA system and of its activators, inhibitors or antagonists is described schematically. The angiotensin II-antagonist 1-sar-8-ala-angiotensin II (Saralasin), when infused in a patient with angiotensinogenic hypertension, induces normalization of the blood pressure during the course of the infusion. The Saralasin infusion test may be of assistance in detecting cases with angiotensinogenic hypertension. The pressor(s) and the extracellular fluid volume appear to be the decisive pathogenetic factors in renal hypertension. As long as the functioning renal mass is sufficient to excrete water and salt normally or in excess, as is the case when the renal perfusion pressure in hypertension is elevated, the pressor is the dominating factor besides other, so far hypothetical mechanism such as the neurogenic. A critical reduction of the renal mass will enhance fluid and salt retention. Thus, an increase in extracellular fluid volume and blood volume will emerge as a major factor inducing hypertension. As a consequence of the volume gain and salt retention, renin secretion may slow down. The possibility is mentioned that the absence or ineffectiveness of renal depressor substances (prostaglandins) may be involved in renal hypertension. Finally, two hypotheses are presented which may explain the finding of LARAGH et al., who grouped their essential hypertensives into 'high, normal and low renin hypertensives'.

Aldosterone↗

PubMed2004

Severe hyperglycemia: a determinant factor for hypofiltration in alloxan diabetic rats.

The relationships among glomerular filtration rate, renal plasma flow and extracellular fluid volume were investigated in control and severely hyperglycemic (442+/-33 mg/dl) untreated, alloxan diabetic ats. Most of diabetic animals showed significant lower values of inulin clearance (diabetics, 0.55+/-0.07 ml/min.100 g; controls, 0.97+/-0.04) and p-aminohippurate clearance (diabetics, 2.11+/-0.39 ml/min.100 g; controls, 3.93+/-0.25). Diabetic rats exhibited reduced efficiency in tubular Na(+) reabsorption, increased urinary Na(+) excretion (diabetics, 3.12+/-0.27 mEq/day; controls, 1.25+/-0.14) and diminished values of plasma renin activity (diabetics, 3.34+/-0.44 ng/ml.h; controls, 8.64+/-0.79). Significant negative correlations were found between glycemia and renal hemodynamic variables. Acute overload with glucose further decreased these variables in both groups: inulin clearance in diabetics vs. controls, 0.26+/-0.04 vs. 0.44+/-0.05 ml/min.100 g; p-aminohippuric acid clearance in diabetics vs. controls, 1.09+/-0.20 vs. 1.55+/-0.21 ml/min.100 g. We conclude that chronically hyperglycemic alloxan diabetic rats showed diminished glomerular filtration rates (inulin clearance), renal plasma flow ( p-aminohippurate clearance) and extracellular fluid volume associated with urinary Na(+) losses and alterations in the renin-angiotensin system. Decreased renin-angiotensin system activity might reduce aldosterone secretion, which in turn could result in (successively) urinary sodium loss, extracellular fluid volume contraction and reductions in glomerular filtration and renal plasma flow.

Animals↗

PubMed2003

Hippocampal vasopressin release evoked by N-methyl D-aspartate (NMDA) microdialysis.

Hippocampus is a brain structure containing vasopressin (AVP) fibers and specific binding sites for this peptide. There is growing evidence that AVP and its metabolites participate in glutamate-mediated plasticity of the hippocampus. The aim of the present study was to evaluate the influence of NMDA on AVP release in the rabbit hippocampus. Caudate nucleus was chosen as the reference structure. The mentioned brain structures were simultaneously microdialyzed with 0.9 % NaCl solution. AVP was determined in the outflowing fluid by radioimmunoassay. The mean basal AVP content in the fluid outflowing from the hippocampus was significantly greater than that from the caudate nucleus. The addition of K(+) into the fluid perfusing the probes implanted into the hippocampus and caudate nucleus significantly increased AVP release into the extracellular fluid of both brain structures. NMDA applied into the mentioned brain structures increased AVP release only from the hippocampus but not from the caudate nucleus. Our findings indicate a role which NMDA receptors play in AVP release into the extracellular fluid of the hippocampus.

Animals↗

PubMed1970

The ontogenesis of haematoencephalic cation transport processes in the rhesus monkey.

1. This investigation was undertaken to determine the time course of development of cation transport processes between blood and the extracellular fluid compartments of the central nervous system (C.N.S.) of the foetal rhesus monkey. The development of concentration gradients within the cerebrospinal fluid (c.s.f.) system was also studied in an attempt to gain information on regional variations in transport activities.2. Cerebrospinal fluid samples were obtained from the lateral ventricle, the cisterna magna, the cortical subarachnoid space and the lumbar region of the spinal subarachnoid space of adult monkeys. Foetal c.s.f. samples were obtained from the cisterna magna and the frontal region of the cortical subarachnoid space. Blood samples were taken within 3-10 min of the c.s.f. samples. The concentration of K, Mg and Ca were determined on appropriately diluted samples by atomic absorption spectrophotometry.3. The concentrations of K, Mg, and Ca in the plasma and c.s.f.s of the adult monkey are similar to those of other mammalian species. The c.s.f./blood concentration gradients of these cations are in the same direction but generally of greater magnitude than those in non-primate mammals. The indicated [Mg] in the extracellular fluid of the adult monkey's cerebral cortex is high (more than 2 m-equiv/kg H(2)O) and the [K] is low (less than 2 m-equiv/kg H(2)O).4. Accumulation of Mg into the c.s.f. system against a concentration gradient is evident in the earliest foetuses studied (50 days of intrauterine life) and by the second half of gestation the concentration gradients of this cation are similar to that of the adult.5. In the second trimester foetus, the [K] in the cisternal fluid is near the plasma ultrafiltrate level. It then decreases gradually throughout the remainder of gestation, approximating the adult value at birth.6. The very low [K] typical of the adult cortical subarachnoid fluid is observed by the sixth month following birth but not during foetal life or within the first few weeks of post-natal life. This indicates that the transport processes at the cortical region of the haematoencephalic interphase do not fully develop until well after birth.7. It is concluded that the various transport processes responsible for the elaboration and maintenance of adult type of K, Ca and Mg concentrations within the extracellular fluid compartments of the monkey C.N.S. do not develop at the same time. This temporal dissociation provides strong evidence against any direct association or coupling between the haematoencephalic K and Mg transport systems.8. Existence of normal cation concentration gradients between c.s.f. and blood may serve as a criterion for the normality of the (foetal) blood-brain barrier.

Age Factors↗

PubMed1976

Intracellular concentrations of the salt gland of the herring gull Larus argentatus.

Attempts were made to measure intra- and extracellular concentrations in secreting and inactive salt gland tissue of the herring gull. 14C-labeled polyethylene glycol (mol wt 4,000) was used as a marker for extracellular fluid. Fluid separated by centrifugation at 36,000 g appeared by three independent criteria to represent primarily extracellular fluid. It could not, however, be fully ascertained if this fluid was mixed with a small amount of intracellular fluid. Therefore, intracellular concentrations were calculated from the concentrations in centrifuged fluid as well as from plasma concentrations. By either method it was found that secreting and inactive glands showed no difference in extracellular and intracellular fluid concentrations of Na, K, Cl and Ca. Secreting glands had lower intracellular water content and a higher intracellular Mg concentration than inactive glands. The absence of evidence for intracellular accumulation of Na and Cl ions in secreting glands suggests that active ion transport takes place across the apical rather than the basal and lateral membranes in spite of the fact that Na-K-activated ATPase is associated with the extensive infoldings of these plasma membranes.

Animals↗

PubMed2003

Mouse hippocampal organotypic tissue cultures exposed to in vitro "ischemia" show selective and delayed CA1 damage that is aggravated by glucose.

Oxygen and glucose deprivation (OGD) in cell cultures is generally studied in a medium, such as artificial cerebrospinal fluid (CSF), with an ion composition similar to that of the extracellular fluid of the normal brain (2 to 4 mmol/L K+, 2 to 3 mmol/L Ca2+; pH 7.4). Because the distribution of ions across cell membranes dramatically shifts during ischemia, the authors exposed mouse organotypic hippocampal tissue cultures to OGD in a medium, an ischemic cerebrospinal fluid, with an ion composition similar to the extracellular fluid of the brain during ischemia (70 mmol/L K+, 0.3 mmol/L Ca2+; pH 6.8). In ischemic CSF, OGD induced a selective and delayed cell death in the CA1 region, as assessed by propidium iodide uptake. Cell death was glutamate receptor dependent since blockade of the N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors mitigated cell damage. Hyperglycemia aggravates ischemic brain damage whereas glucose in artificial CSF prevents oxygen deprivation-induced damage. The authors demonstrate that glucose in ischemic CSF significantly exacerbates cell damage after oxygen deprivation. This new model of "ischemia" can be useful in future studies of the mechanisms and treatment of ischemic cell death, including studies using genetically modified mice.

Animals↗

PubMed1994

Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide.

The presence of bioactive interleukin-1 (IL-1) in various brain regions (cerebellum, cortex, brainstem, diencephalon or hippocampus) after either intraperitoneal (i.p.) or intraventricular (i.c.v.) injection of lipopolysaccharide (LPS) was studied in the rat. To detect IL-1, extracellular fluid and cell lysate were fractionated by gel exclusion chromatography and fractions tested for thymocyte stimulation; presence of IL-1 was confirmed by blockade of stimulation by addition to the assay of a monoclonal antibody (mAb) to IL-1 receptor. When LPS was infused i.c.v., IL-1 was detected in the brainstem and diencephalon 2 h after injection, and in all the brain regions except cerebellum 6 h after injection; IL-1 was not detected in the plasma of these animals. When LPS was injected i.p., IL-1 was detected in the plasma but not in the brain 2 h after the injection, and in all brain regions but not in the plasma 6 h after the injection. In all of these cases, IL-1 was found in extracellular fluid; in some cases (cortex, cerebellum) cell lysate of the region did not produce detectable bioactivity, thereby indicating that IL-1 in these brain regions is processed to active peptide during release, as has been reported in the periphery. In those cases where bioactivity was detected in cell lysate (brainstem, diencephalon), bioactivity was not blocked by IL-1 receptor mAb, indicating presence of a non-IL-1 stimulating factor. These results further support the idea that IL-1 is secreted by cells in the brain, and indicate that it is found in the extracellular fluid of many brain regions following an appropriate stimulus in the periphery as well as in the brain.

Animals↗

PubMed1993

Characterization of antigen-presenting cells that present exogenous antigens in association with class I MHC molecules.

Exogenous Ag in the extracellular fluids do not gain access to the class I Ag-presenting pathway in most cells. However, there is an APC resident in spleen that can process and present exogenous Ag in association with class I molecules. We characterize the phenotype of this cell. This APC is of low buoyant density, is adherent to Sepharose and glass, and expresses both class II molecules and FcR. This phenotype identifies this APC as a macrophage. Resident, peptone- and thioglycolate-induced peritoneal macrophages also display this Ag-presenting activity. Analysis with CTL clones suggest that this Ag-presenting pathway may be active in only a subset of macrophages. A similar Ag-presenting activity is also present in dendritic cell-enriched populations from spleen although we cannot rule out the possible involvement of contaminating macrophages. In contrast, B and T cells that are resident in spleen and LPS blasts are unable to present exogenous Ag in association with class I molecules. The presentation of exogenous OVA with class I molecules is not inhibited by the inhibitors of thiol proteases, leupeptin, and antipain. The presence of gelonin, a ribosomal inactivating protein, in the extracellular fluids inhibits the ability of these APC to present exogenous OVA. Under identical conditions, gelonin does not inhibit Con A-stimulated T cell proliferation, or LPS-stimulated B cell proliferation and Ag presentation. These results are discussed in relation to the potential pathways through which an Ag in the extracellular fluids is presented with MHC class I molecules.

Animals↗

PubMed1998

Skeletal muscle ECF pH error signal for exercise ventilatory control.

An autonomic reflex linking exercising skeletal muscle metabolism to central ventilatory control is thought to be mediated by neural afferents having free endings that terminate in the interstitial fluid of muscle. To determine whether changes in muscle extracellular fluid pH (pHe) can provide an error signal for exercise ventilatory control, pHe was measured during electrically induced contraction by 31P-magnetic resonance spectroscopy and the chemical shift of a phosphorylated, pH-sensitive marker that distributes to the extracellular fluid (phenylphosphonic acid). Seven lightly anesthetized rats underwent unilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-T nuclear magnetic resonance magnet, which resulted in a mixed lactic acidosis and respiratory alkalosis, with no net change in arterial pH. Skeletal muscle intracellular pH fell from 7.30 +/- 0.03 units at rest to 6.72 +/- 0.05 units at 2.4 min of stimulation and then rose to 7.05 +/- 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction. Despite arterial hypocapnia, pHe showed an immediate drop from its resting baseline of 7.40 +/- 0.01 to 7.16 +/- 0.04 units (P < 0.05) and remained acidic throughout the stimulation protocol. During the on- and off-transients for 5-Hz stimulation, changes in the pH gradient between intracellular and extracellular compartments suggested time-dependent recruitment of sarcolemmal ion-transport mechanisms. pHe of exercising skeletal muscle meets temporal and qualitative criteria necessary for a ventilatory metaboreflex mediator in a setting where arterial pH does not.

Acid-Base Equilibrium↗

PubMed1988

NMR of skeletal muscle. Differences in relaxation parameters related to extracellular/intracellular fluid spaces.

The relationships between the T1 and T2 relaxation times, tissue water content and extracellular fluid space of two types of skeletal muscle groups were studied in rabbits and rats by means of NMR proton spectroscopy (10 MHz). Although there was no significant difference in the total water content between muscles rich in type I (74.5 +/- .8%; soleus) or type II (75.0 +/- .7%; gastrocnemius) fibers, the respective T1 (521 +/- 25 vs. 486 +/- 16 millisecond; p less than .01) and T2 (39.5 +/- 1.8 vs. 36.5 +/- 1.0 millisecond; p less than .01) relaxation times were consistently prolonged. The longer relaxation times of the soleus as compared with the gastrocnemius muscle were related to a larger extracellular fluid space as measured by (35S) sulfate +34.5%; p less than .01). For this reason, it seems likely selective changes in these spaces will be detectable by NMR proton imaging.

Animals↗

PubMed1986

The movement of fluids and substances in the testis.

Three aspects of the control of movements of fluids and substances into, out of and inside the testis are discussed: the tubular barrier, the interstitial extracellular fluid and the testicular blood vessels. The functional basis for the tubular barrier is twofold; there are significant differences in the concentration of many substances inside and outside the tubules and marker substances enter or leave the tubular fluid at widely different rates, depending on lipid solubility and the presence of specific carrier systems. The anatomical basis for this barrier appears to be the specialized junctions between adjacent pairs of Sertoli cells. The barrier develops only at puberty, as the first cells undergo meiosis, but the development may not be as sudden as previously believed. The barrier breaks down after efferent duct ligation when spermatogenesis is disrupted. Techniques for measuring the volume, the turnover rate, the composition and fate of the interstitial extracellular fluid are described, and the unsatisfactory features of the presently available techniques for collecting this fluid for analysis are emphasized. There is a relationship between the fluid in the testis and lymph from vessels in the spermatic cord and lymph may be important for the transport of hormones to the general circulation in some circumstances and to other organs close to the testis. The testicular blood vessels display certain unusual features, a very high susceptibility to the toxic effects of cadmium salts, a high level of alkaline phosphatase activity in all endothelial cells but only after puberty and a high level of gamma-glutamyl transpeptidase in the endothelial cells of the arterioles and the testicular artery. These same cells are the site for a specific transport system for leucine and phenylalanine, with kinetic characteristics similar to the system in brain. Flow of blood may limit hormone secretion by the aspermatogenic testis, but diffusion limitation may also be important under some circumstances. A fuller understanding of the ways in which substances move around in the testis, particularly how they cross the endothelial cell layer or penetrate into the tubules, will be important for a better appreciation of testicular function.

Animals↗

PubMed1985

Diffusible sodium, potassium, magnesium, calcium and phosphorus in frog skeletal muscle.

A microvolumetric analytical method has been developed to measure the endogenous concentrations of diffusible elements in muscle cells. Single twitch fibres from frog muscle were skinned under oil and 0.2 nl drops of isosmotic sucrose solution, held in the tips of specially constructed pipettes, were placed in contact with the skinned fibres. After 0-10 min, the microdrops were removed and analysed with a wave-length dispersive X-ray spectrometer. The uptake of Na, K, Mg, and P into the microdrops was well fitted by a single exponential function, while the uptake of Ca was better represented by the sum of two exponential functions. All elements analysed except Ca reached diffusional equilibrium within 5 min of placing the microdrop on the fibre, while Ca was still not equilibrated at 10 min. For freshly isolated muscle fibres, diffusible element concentrations in the microdrops at equilibrium were (in mM, mean +/- S.D.): Na, 7.6 +/- 7.2; K, 82 +/- 36; Mg, 5.8 +/- 3.0; P, 51 +/- 19. Diffusible Ca concentration (at 10 min elapsed sampling time) was 0.7 +/- 0.4 mM. Results from experiments in which microdrops were equilibrated with skinned fibres pre-soaked in an artificial (Ca-free) solution support the notion that the exogenous solutes can replace the endogenous diffusible contents of a skinned fibre by soaking the skinned fibre in a relatively large volume of the artificial solution. Total Na, K, Mg, Ca, and P content of whole muscle was measured by electron probe analysis of muscle extracts. In freshly isolated muscle, whole muscle element content was (in mmol/kg wet weight, mean +/- S.D.): Na, 21 +/- 8; K, 120 +/- 26; Mg, 9.7 +/- 2.6; Ca, 2.2 +/- 0.5; P, 76 +/- 18. Extracellular fluid volumes of freshly isolated whole muscles were estimated by compartmental analysis of Na efflux. Extracellular element concentrations were measured by electron probe analysis of frog plasma. Using the extracellular fluid volume and concentration estimates, extracellular contributions were subtracted from measurements of the element content of whole muscle to yield estimates of total intracellular element concentration (in mmol/l myoplasmic water). Based on the values for the intracellular total and diffusible element concentrations, the diffusible/total content fraction in freshly isolated muscle is estimated to be: Na, 0.38; K, 0.48; Mg, 0.42; Ca, 0.22; and P, 0.47.

Animals↗

PubMed1985

Maintenance of blood volume in snakes: transcapillary shifts of extravascular fluids during acute hemorrhage.

Tracer dilution analysis (D2O, 51Cr, and NaS14CN) was used to investigate the steady-state compartmentation of body fluids and the extent of fluid transfer from extravascular to vascular spaces during hemorrhage-induced hypovolemia in two species of snakes, Elaphe obsoleta and Crotalus viridis. Fluid spaces of the two species are not significantly different (means, blood volume 6.1, 5.4; extracellular fluid 42.2, 41.9; total body water 77.2, 77.2% body mass, respectively), but values for extracellular fluid exceed those reported for other reptiles. Both species of snake withstand graded hemorrhage where 4% of the initial blood volume is withdrawn every 10 min until the cumulative deficit is 32%. Some snakes are able to maintain their initial blood volume throughout hemorrhage, while others restore 90% of deficits within 2 h after hemorrhage ceases. Typically, 50-60% of the hemorrhaged deficit is transferred from the interstitium to the circulation throughout hemorrhage (Fig. 2). The source of fluid entering the vascular space is entirely extracellular during hemorrhage, the blood within 2 h after hemorrhage ceases. Snakes are able to maintain arterial pressure during these experiments (Fig. 3). The ability of snakes to maintain hemodynamic stability despite substantial losses of blood can be explained in terms of a large interstitial fluid volume that may shift rapidly to the vascular space. Shifts in the opposite direction also occur in response to hemodynamic factors, implying a low resistance to fluid movement across the capillary wall.

Animals↗

PubMed1997

Mechanisms attenuating cellular responses to neuropeptides: extracellular degradation of ligands and desensitization of receptors.

Neuropeptides make up one of the largest and functionally most diverse groups of signaling molecules. They exert their effects by interacting with members of the large family of G-protein-coupled receptors, which transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins. Cellular responses to neuropeptides are usually rapidly attenuated. Mechanisms of signal attenuation include removal of peptides from the extracellular fluid and receptor desensitization. Peptides are removed from the extracellular fluid principally by enzymatic degradation by cell surface enzymes, exemplified by neutral endopeptidase. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second messenger kinases, interaction of receptors with arrestins, and consequent receptor uncoupling from G-proteins. Peptides also induce endocytosis of their receptors, which may contribute to desensitization by depleting the cell surface of high-affinity receptors. Recycling and processing of internalized receptors, which include dissociation of receptors from their ligands and receptor dephosphorylation, contribute to resensitization of cellular responses. These regulatory mechanisms are important for they determine the ability of cells to respond to agonists, and defects may result in uncontrolled stimulation of cells, which could cause disease. A greater understanding of the processes that modulate signaling by neuropeptides may lead to the development of novel receptor antagonists and agonists and help to explain the mechanism of drug tolerance.

Animals↗

PubMed1991

8-hydroxy-2-(di-N-propylamino)tetralin increases the activity of adenylate cyclase in the hippocampus of freely-moving rats.

The present study was designed to examine the effects of intraperitoneal (i.p.) administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on the efflux of cyclic adenosine monophosphate (cAMP) in the extracellular fluid of the dorsal hippocampus, using in vivo microdialysis. One week after implantation of the guide, probes were inserted in conscious rats and perfused with Ringer solution. Steady basal levels of cAMP (2.9 +/- 0.1 pmol/ml, n = 74 rats) were obtained after at least three hours of stabilisation. The 8-OH-DPAT dose-dependently increased the basal efflux of cAMP, which was most apparent between 20-40 min after the injection. The largest dose of 8-OH-DPAT (1 mg/kg) tested, induced a maximum response of approximately 50%, whereas injections of saline did not alter the efflux of cAMP. Treatment with (+/-)pindolol (10 mg/kg) did not significantly affect the basal efflux of cAMP, whereas it markedly inhibited the increase in levels of cAMP, induced by 0.5 mg/kg 8-OH-DPAT (injected 40 min later). Simultaneous behavioural observations demonstrated that (+/-)pindolol also attenuated various components of the 8-OH-DPAT-induced behavioural syndrome. Addition of 3-isobutyl-1-methylxanthine (IBMX), forskolin or noradrenaline, to the perfusion fluid, strongly enhanced the levels of cAMP in the extracellular fluid from the hippocampus. Injection of 8-OH-DPAT (1 mg/kg) during perfusion with IBMX induced a similar increase in levels of cAMP, as under normal perfusion conditions. However, 8-OH-DPAT did not significantly alter the efflux of cAMP, when probes were perfused with either forskolin or forskolin and IBMX.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗