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PubMed1987

Cross-linking of immune complexes by human mononuclear phagocytes.

Incubation of immune complexes (IC) bound to plastic surfaces with human blood monocytes for 48 hours resulted in the cross-linking of a proportion of antibody molecules. This process was largely inhibited by the addition of sodium azide to the cultures. Cross-linking was defined as the inability of strong chaotropic solutions (3 M MgCl2 or 5 M guanidine) or acid pH (0.1 N HCl) to solubilize 125I-labeled rabbit anti-human serum albumin attached to plastic-bound antigen. Addition to the cultures of a suitable hydrogen donor such as catechol (0.5 mM) resulted in a large increase in cross-linking of IC. This process was shown to depend on the presence of viable phagocytic cells because incubation with dead monocytes or with viable T lymphocytes failed to induce cross-linking. Quantitation of rabbit immunoglobulin remaining in the wells by enzyme-linked immunoassay techniques excluded the possibility that the increase in 125I bound was merely due to a transiodination reaction. Experiments using various oxygen metabolite inhibitors and scavengers indicated that catechol-dependent protein cross-linking depended on the action of hydrogen peroxide and enzyme systems inhibitable by sodium azide, probably monocyte-peroxidase. Superoxide dismutase, 1O2, and OH X radical scavengers failed to inhibit cross-linking, whereas addition of catalase resulted in almost complete abolition of the process. These observations suggest that catechol-dependent cross-linking of IC may be due to oxidation of catechol to orthoquinone and that this strong oxidant is responsible for nonenzymic chemical action on proteins leading to intermolecular covalent bond formation. Cell-mediated protein cross-linking by oxidative mechanisms may be a prominent feature of drug-related reactions and of acute and chronic inflammatory processes in general. The possible mechanisms involved in catechol-dependent and -independent cross-linking of IC by human mononuclear phagocytes are discussed.

Antigen-Antibody Complex↗

PubMed1999

Responses to hypoxia of petrosal ganglia in vitro.

NaCN is a classical stimulus used to elicit discharges from carotid body chemoreceptors. The effect is assumed to be mediated by glomus (type I) cells, which release an excitatory transmitter for the excitation of carotid nerve endings. Since the sensory perikarya of the glossopharyngeal nerve (from which the carotid nerve branches) are located in the petrosal ganglion, we tested whether application of this drug to the petrosal ganglion superfused in vitro elicits antidromic discharges in the carotid nerve. NaCN did indeed cause an intense and prolonged burst of nerve impulses in the carotid nerve, while provoking a less intense and much briefer burst of discharges in the glossopharyngeal branch. Carotid nerve responses to NaCN were reduced and shortened by prior or following application of dopamine to the ganglion. Sodium azide applied to the petrosal ganglion evoked a less intense and much briefer burst of impulses in the carotid nerve. Ganglionar application of 2,4-dinitrophenol did not induce discharges in the carotid nerve. Switching the superfusion of the ganglion from a normoxic to a hypoxic solution did not evoke discharges in the carotid nerve. Therefore, the perikarya of carotid nerve neurons are sensitive to NaCN, but are not excited by reducing the pO(2) of the superfusing solution.

2,4-Dinitrophenol↗

PubMed2003

pH and energy dependent transport of ketoprofen across rat jejunum in vitro.

The aim of this study was to elucidate transport mechanisms of ketoprofen (monocarboxylic acid with pK(a) 4.6) across rat jejunum in vitro using side-by-side diffusion cells. When the tissue was incubated on the mucosal and serosal sides with buffer of pH 7.51 (pH of the mucosal surface was 7.08), ketoprofen permeated faster in the mucosal-to-serosal than in the opposite direction. No asymmetry in transport was observed when 2 mM mucus disrupting agent 1,4-dithio-DL-threitol (pH of the mucosal surface increased to 7.21) was added to the mucosal side. Mucosal-to-serosal permeability of ketoprofen increased three times when the pH of the incubation medium was changed from 8.06 (pH of the mucosal surface was 7.34) to 6.07 (pH of the mucosal surface was 5.95), while no pH dependence was found under ATP-depletion caused by sodium azide. In the ketoprofen concentration range from 0.125 to 5 mM no saturation of transport was observed. Moreover, ketoprofen transport was not changed in the presence of 2 mM benzoate, 10 and 20 mM acetate, 20 mM L-lactate (substrates for monocarboxylate transporter 1, MCT1) and 1 mM alpha-cyano-4-hydroxy-cinnamic acid (an inhibitor of MCT1). These results indicate that ketoprofen is transported across rat jejunum in vitro by pH and energy dependent transport mechanisms, and most probably not by MCT1.

Adenosine Triphosphate↗

PubMed2003

[The inhibitory effect of Lu-Duo-Wei on carbon disulfide-induced generation of hydroxyl radicals].

OBJECTIVE: To study the scavenging effects of Lu-Duo-Wei, thiourea, superoxide dismutase, and sodium azide on carbon disulfide-induced generation of hydroxyl radicals. METHODS: Phenanthroline-CuSO(4)-Vit C-H(2)O(2) chemiluminescence system (PHEN system) containing alcohol was established to probe the influence of various concentrations of carbon disulfide on hydroxyl radicals emission intensity and the scavenging effects of Lu-Duo-Wei and other antioxidants on carbon disulfide-induced hydroxyl radicals were observed. RESULTS: The average emission intensity of PHEN system containing alcohol appeared lower luminescence [91.03 x 10(3) (cp6s)] and longer time (75 s) to get the peak than the system without alcohol [96.11 x 10(3) (cp6s), 55 s]. The specific scavenger of hydroxyl radical, thiourea, showed clear inhibitory effect on the system. Carbon disulfide in the range of 40 - 160 mmol/L promoted the generation of hydroxyl radical, however, this effect could be efficiently inhibited by thiourea. 160 mmol/L carbon disulfide in PHEN system without copper seemed as an activator to promote the luminescence, while in PHEN system withdrawing phenanthroline appeared some weak action of luminescence agent at low concentration. Meanwhile, Lu-Duo-Wei may efficiently scavenge hydroxyl radicals induced by carbon disulfide in PHEN system but superoxide dismutase and sodium azide had little effects on the system. CONCLUSION: Carbon disulfide may induce PHEN system to generate hydroxyl radicals and Lu-Duo-Wei may efficiently scavenge these free radicals and play an important role in protection against oxidative injury induced by carbon disulfide.

Carbon Disulfide↗

PubMed1991

Hypoxia induces endothelial cell synthesis of membrane-associated proteins.

Hypoxemia is associated with a prothrombotic tendency. In this study we report the purification and partial characterization of an activator of a central coagulation component, factor X, induced in endothelium by exposure to hypoxia (hypoxia-induced factor X activator or Xact). Expression of Xact occurred in a reversible manner when endothelial cell cultures were exposed to hypoxia or sodium azide but not in response to a variety of other alterations in the cellular milieu, such as heat shock or glucose deprivation. The activity of Xact, which was not detected in normoxic endothelial cells, was maximal under acidic conditions, pH 6.0-6.8, which often coexist with hypoxia in an ischemic milieu. By sequential isoelectric focusing and preparative SDS/PAGE of endothelial membrane-rich fractions, Xact was purified approximately 19,000-fold and found to be a single-chain, approximately 100-kDa polypeptide with pI approximately 5.0. Activation of factor X by purified Xact was not affected by blocking antibodies to other coagulation proteins or by phenylmethylsulfonyl fluoride or leupeptin but was prevented by mercury chloride or iodoacetamide. In addition to the induction of Xact, two-dimensional gel analysis of membrane fractions from metabolically labeled hypoxic endothelial cultures revealed two groups of approximately 10 additional spots: (i) a group for which expression was maximal after 24 hr and (ii) a group for which expression continued to increase up to 48 hr. The pattern of hypoxia-mediated modulation of protein expression was distinct from that seen with other cellular stimuli but could be duplicated, in part, by sodium azide. These results indicate that hypoxia elicits a specific biosynthetic response, including the expression of endothelial cell-surface molecules that can alter cellular function and may potentially serve as markers of hypoxemic vessel-wall injury.

Animals↗

PubMed1986

The effects of dim cyclic light on pigment epithelial function in the albino rat.

Most pathologies of the outer retina include physiological and morphological changes in the pigment epithelium. The question of pigment epithelial involvement in retinal light damage caused by low intensities of light is still unresolved. In the present study, we investigated the effects of low intensity cyclic light on pigment epithelial function in albino rats. The functioning of the pigment epithelium was assessed electrophysiologically from d.c. recordings of ERG c-waves and sodium azide induced changes in the resting potential. Responses obtained from albino rats raised under low intensity cyclic light (0.63 ft cd. 12:12 L:D) were compared to those obtained from albino rats raised under minimal light exposure conditions (dark-reared) and pigmented rats housed under low intensity cyclic light. We report, for the first time, that albino rats raised from birth under low intensity cyclic light possess c-waves. Their responses were comparable in amplitude and latency to those recorded from pigmented rats housed under similar conditions, but were significantly smaller than those recorded from dark-reared albino rats. The reduction in the amplitudes of the c-waves recorded from cyclic light-reared albino rats was probably not due to retinal light damage. Comparisons of the amplitudes and latencies of ERG b-waves recorded from cyclic light-reared and dark-reared albino rats did not suggest that the retinas of the cyclic light-reared albino rats had been damaged by light. Light microscopic examination of these retinas also provided no evidence for light damage. The transient, positive potential changes recorded from cyclic light-reared albino rats in response to bolus injections of sodium azide were significantly smaller than those recorded from either dark-reared albino rats or pigmented rats housed under low intensity cyclic light. The results of these experiments suggest that the pigment epithelium of albino rats is functionally altered by extremely low intensities of cyclic light.

Albinism↗

PubMedDate not supplied

[Effect of cytochrome oxidase inhibitors on the yeast thermotolerance].

The investigation of the effect of the cytochrome oxidase inhibitors sodium cyanide and sodium azide on the thermotolerance of the yeasts Rhodotorula rubra, Debaryomyces vanriji, and Saccharomyces cerevisiae showed that these inhibitors diminish the thermotolerance of R. rubra and D. vanriji, but do not affect the thermotolerance of S. cerevisiae. Taking into account the fact that, unlike the latter yeast, R. rubra and D. vanriji are nonfermentative yeasts, the difference in the effects of the inhibitors on the yeast thermotolerance can be readily explained by the different types of glucose utilization (either oxidative or fermentative) in these yeasts. The data obtained also provide evidence that there is a correlation between the functional activity of mitochondria and the thermotolerance of yeast cells.

Adaptation, Physiological↗

PubMed2002

Resistance of isolated mammalian spinal cord white matter to oxygen-glucose deprivation.

We found that isolated guinea pig spinal cord white matter is resistant to acute oxygen-glucose deprivation. Sixty minutes of oxygen-glucose deprivation resulted in a 60% reduction of compound action potential (CAP) conductance, and there was a near complete recovery after 60 min reperfusion. Corresponding horseradish peroxidase-exclusion assay showed little axonal membrane damage. To further deprive the axons of metabolic substrate, we added 2 mM sodium cyanide or 2 mM sodium azide, both mitochondrial suppressors, to the ischemic medium, which completely abolished CAP and resulted in a 15 to approximately 30% recovery postreperfusion. Both compounds preferentially reduced the conductance of large diameter axons. We suggest the residual ATP in our ischemic model can protect anatomic integrity and physiological functioning of spinal axons following ischemic insult. This further suggests that oxygen-glucose deprivation alone cannot be solely responsible for short-term functional and anatomic damage. The damaging effects of ischemia in vivo may be mediated by factors originating from the gray matter of the cord or other systemic factors; both were largely eliminated in our in vitro white matter preparation.

Action Potentials↗

PubMed1988

Endothelium-derived relaxing factor and atriopeptin II elevate cyclic GMP levels in pig aortic endothelial cells.

1. Two directly-acting stimulants of soluble guanylate cyclase, glyceryl trinitrate (0.1 microM) and sodium azide (10 microM), and a receptor-mediated stimulant of particulate guanylate cyclase, atriopeptin II (10 nM), each elevated the cyclic GMP content of primary cultures of pig aortic endothelial cells without affecting the cyclic AMP content. 2. Two receptor-mediated stimulants of adenylate cyclase, glucagon (1 microM) and isoprenaline (10 microM), had no effect on the cyclic AMP or cyclic GMP content of these cells, but the directly acting stimulant, forskolin (30 microM), induced a small increase in cyclic AMP content. 3. Three agents that release endothelium-derived relaxing factor (EDRF); bradykinin (0.1 microM), ATP (10 microM) and ionophore A23187 (0.1 microM), each markedly elevated the cyclic GMP content of pig aortic endothelial cells, but acetylcholine (1 microM) had no effect. None of these agents had any effect on cyclic AMP content. 4. Two agents that potentiate the actions of EDRF; M & B 22948 (100 microM) and superoxide dismutase (30 units ml-1), each elevated the cyclic GMP content of pig aortic endothelial cells without affecting the cyclic AMP content. Pretreating cells with catalase (100 units ml-1) did not affect the rise in cyclic GMP content induced by superoxide dismutase (30 units ml-1). 5. Pretreatment of pig aortic endothelial cells with haemoglobin (10 microM) reduced the resting content of cyclic GMP and blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 microM), sodium azide (10 microM), bradykinin (0.1 microM), ATP (10 microM), ionophore A23187 (0.1 microM), M & B 22948 (100 microM) and superoxide dismutase (30 units ml-1), but not that induced by atriopeptin II (10 nM). 6. Pretreatment of pig aortic endothelial cells with an inhibitor of soluble guanylate cyclase, methylene blue (20 microM), had no effect on the resting content of cyclic GMP. Methylene blue (20 microM) blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 microM), M & B22948 (100 microM) and bradykinin (0.1 microM), but not that induced by atriopeptin II (10 nM). 7. The data show that soluble guanylate cyclase, particulate guanylate cyclase and adenylate cyclase are present in pig aortic endothelial cells. They further suggest that EDRF, produced spontaneously or in response to vasoactive agents, elevates endothelial cyclic GMP content by stimulating soluble guanylate cyclase. It is possible that this may serve as a feedback loop by which the endothelial cell modulates EDRF production.

Adenylyl Cyclases↗

PubMed2004

Modification of sheep plasma kininogen by free radicals.

Riboflavin sensitized photodynamic modifications of high molecular weight Kininogen (HMWK) isolated from sheep (Avis-arias) plasma leads to inactivation of antiproteinase activity and formation of aggregated products. A continued disappearance of the inhibitory activity towards papain and formation of high molecular weight adducts was observed with increasing concentration of riboflavin and varying time periods of incubation reaching a maximum value of over 85% (loss in activity). Aggregates resisted dissociation upon heating at 100 degrees C in 1% SDS. Aggregation and photoinactivation of HMWK was promoted by the substitution of H2O for deuterium oxide (D2O), which is known to prolong the life span of singlet oxygen, and suppressed by sodium azide a known singlet oxygen quencher. Mannitol and thiourea (hydroxyl radical scavenger) did not protect the antiproteinase activity of HMWK. Treatment with reducing agent resulted in decrease of the aggregated products suggesting the possible involvement of disulfide linkages in protein crosslinking. Tryptophan fluorescence was completely lost and significant production of dityrosine was detected in photoinactivated HMWK aggregates. Changes in the far Ultra violet circular dichroism (u.v.c.d.) spectrum of HMWK was indicative of loss of secondary structure. Analysis of modifications induced in HMWK by riboflavin reveals that the processes proceed via a singlet oxygen mediated pathway. It is concluded that the susceptibility of HMWK to oxidation may arise from oxidative modifications by reactive oxygen species generated in plasma.

Animals↗

PubMedDate not supplied

In vitro cytochemical studies of the golgi apparatus of pancreatic acinar cells exposed to drugs that inhibit the transport of membranes and proteins.

In a preceding article, we described alterations occurring in rat pancreas acinar cells at successive post-mortem (PM) intervals. In ultra-thin sections from samples obtained from 0.5, 1, 2, 4, 8 and 12 h, we observed in the Golgi apparatus the appearance of an anomalous membrane bound structure. Such structures are formed by tubules and vesicles that we have called tubular vesicular structure (TVS), and they are frequently located in the position corresponding to the 4th cisterna of the Golgian cisternal pile. Lobules of rat pancreas, incubated in vitro with metabolic inhibitors (such as antimycin A, sodium fluoride, sodium azide and potassium cyanide), were processed in order to be compared with the PM samples of the rat acinar cells. In sliced pieces of lobules, acid phosphatase (AcPase) and tiaminopirophosphatase (TPPase) activity were evaluated. Except for the potassium cyanide treatment, we frequently observed the TVS located at the position corresponding to the 4th cisternae (similar to those observed in the PM acinar cells). These TVS's are predominantly TPPase positive. Based on this result and the fact that the TVS's are surrounded by a membrane (as confirmed by the freeze-fracture replica results) with no structural elements inside, they seem not to correspond to autophagosomes. The TVS's, observed either at PM consecutive times or incubated with metabolic inhibitors, seem to be structures formed in response to ATP deprivation. In 0,5 h PM cells and in cells incubated for 30 and 60 min with metabolic inhibitors, the subcellular structures reacted for AcPase in the rigid lamellae, CV and lysosomes.

Acid Phosphatase↗

PubMed2002

A rice mutant defective in Si uptake.

Rice (Oryza sativa) accumulates silicon (Si) in the tops to levels up to 10.0% of shoot dry weight, but the mechanism responsible for high Si uptake by rice roots is not understood. We isolated a rice mutant (GR1) that is defective in active Si uptake by screening M(2) seeds (64,000) of rice cv Oochikara that were treated with 10(-3) M sodium azide for 6 h at 25 degrees C. There were no phenotypic differences between wild type (WT) and GR1 except that the leaf blade of GR1 remained droopy when Si was supplied. Uptake experiments showed that Si uptake by GR1 was significantly lower than that by WT at both low and high Si concentrations. However, there was no difference in the uptake of other nutrients such as phosphorus and potassium. Si concentration in the xylem sap of WT was 33-fold that of the external solution, but that of GR1 was 3-fold higher than the external solution at 0.15 mM Si. Si uptake by WT was inhibited by metabolic inhibitors including NaCN and 2,4-dinitrophenol and by low temperature, whereas Si uptake by GR1 was not inhibited by these agents. These results suggest that an active transport system for Si uptake is disrupted in GR1. Analysis of F(2) populations between GR1 and WT showed that roots with high Si uptake and roots with low Si uptake segregated at a 3:1 ratio, suggesting that GR1 is a recessive mutant of Si uptake.

2,4-Dinitrophenol↗

PubMed2006

Sigma-1 receptor activation prevents intracellular calcium dysregulation in cortical neurons during in vitro ischemia.

Sigma receptors are putative targets for neuroprotection following ischemia; however, little is known on their mechanism of action. One of the key components in the demise of neurons following ischemic injury is the disruption of intracellular calcium homeostasis. Fluorometric calcium imaging was used to examine the effects of sigma receptor activation on changes in intracellular calcium concentrations ([Ca(2+)](i)) evoked by in vitro ischemia in cultured cortical neurons from embryonic rats. The sigma receptor agonist, 1,3-di-o-tolyl-guanidine (DTG), was shown to depress [Ca(2+)](i) elevations observed in response to ischemia induced by sodium azide and glucose deprivation. Two sigma receptor antagonists, metaphit [1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine] and BD-1047 (N-[2-3,4-dichlorophenyl)-ethyl]-N-methyl-2-(dimethylamino)ethylamine), were shown to blunt the ability of DTG to inhibit ischemia-evoked increases in [Ca(2+)](i), revealing that the effects are mediated by activation of sigma receptors and not via the actions of DTG on nonspecific targets such as N-methyl-d-aspartate receptors. DTG inhibition of ischemia-induced increases in [Ca(2+)](i) was mimicked by the sigma-1 receptor-selective agonists, carbetapentane, (+)-pentazocine and PRE-084 [2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate hydrochloride], but not by the sigma-2-selective agonist, ibogaine, showing that activation of sigma-1 receptors is responsible for the effects. In contrast, DTG, carbetapentane, and ibogaine blocked spontaneous, synchronous calcium transients observed in our preparation at concentrations consistent with sigma receptor-mediated effects, indicating that both sigma-1 and sigma-2 receptors regulate events that affect [Ca(2+)](i) in cortical neurons. Our studies show that activation of sigma receptors can ameliorate [Ca(2+)](i) dysregulation associated with ischemia in cortical neurons and, thus, identify one of the mechanisms by which these receptors may exert their neuroprotective properties.

Analgesics, Opioid↗

PubMed1996

Elucidating the mechanism of cortical microtubule reorientation in plant cells.

Reorientation of the cortical microtubule array is an essential component of cellular development in plants. However, mechanistic details of this process are unknown. The cortical microtubule array of freshly isolated protoplasts (obtained from Nicotiana tabacum BY-2 suspension culture) is relatively random, but upon culturing the cell wall regenerates and the microtubules begin to reorganize. Because cortical microtubules are highly dynamic, we postulated that their reorganization is accomplished solely by the depolymerization of disordered microtubules, followed by repolymerization into an ordered array. This hypothesis was tested on freshly isolated protoplasts using drugs that alter the dynamic status of microtubules by either hyperstabilizing the polymer (taxol); or preventing the addition of subunits to the microtubules (amiprophosmethyl; APM). Microtubule arrays that were hyperstabilized with 10 microM taxol not only reordered, but did so more quickly than untreated cells. Moreover, protoplasts treated with taxol and 20 microM APM also showed accelerated reorganization. Control experiments, performed in vivo and in vitro, confirmed that subunit addition was hindered by APM. Thus, microtubules appear capable of reorienting as relatively intact units. Sodium azide (1 mM) and sodium cyanide (1 mM) can prevent reorientation, indicating that cellular energy is required for this event but this energy is not used by the actin-myosin system because the microfilament-disrupting drug cytochalasin D (50 microM) did not affect reorientation. These results indicate that cortical microtubule array reorganization is a complex process that can involve polymer movement.

Cell Movement↗

PubMed2004

Modulation of intestinal P-glycoprotein function by cremophor EL and other surfactants by an in vitro diffusion chamber method using the isolated rat intestinal membranes.

Effects of various surfactants on the transport of rhodamine123, a P-glycoprotein (P-gp) substrate, across the isolated rat intestinal membranes were examined by an in vitro diffusion chamber system. The jejunal serosal-to-mucosal transport (Jsm) of rhodamine123 was more than threefold greater than its mucosal-to-serosal transport (Jms), suggesting that the net movement of rhodamine123 across the rat jejunum was preferentially secretory direction. There exists a regional difference in the intestinal transport of rhodamine123 and the secretory directed transport was remarkably observed in the jejunum. The Jsm/Jms ratio of rhodamine123 decreased in the presence of 0.3 mM verapamil and 10 mM sodium azide (NaN3) + 1 mM sodium fluoride (NaF), confirming that rhodamine123 might be secreted from the intestinal tissue into the lumen by a P-gp-mediated efflux system. Nonionic surfactants [0.1% Cremophor EL, Tween 80 and n-dodecyl-beta-D-maltopyranoside (LM)] reduced the Jsm/Jms ratio of rhodamine123, whereas its ratio was not influenced in the presence of 0.1% cationic surfactant (hexadecyltrimethylammonium bromide, C16TAB) and anionic surfactant (sodium dodecyl sulfate, SDS). Therefore, these findings suggested that charge of surfactants was possibly related to the action of these surfactants on the intestinal absorption of P-gp substrates. On the other hand, the transfer of rhodamine123 was not affected by the addition of Cremophor EL to the serosal side. Because the c.m.c. of Cremophor EL is 0.0095 w/v%, interactions between rhodamine123 and the micellar form of Cremophor EL may decrease the P-gp-mediated efflux of rhodamine123 at higher concentrations. In the kinetic analysis, the Vmax value (nmol/min/g wet tissue) of rhodamine123 decreased, although the Km value (mM) was constant in the presence of Cremophor EL. Therefore, Cremophor EL inhibited the efflux transport of rhodamine123 in a noncompetitive manner. Cremophor EL did not affect the transport of [14C]Gly-Sar and [3H]3-O-methyl-D-glucose, suggesting that the action of Cremophor EL might be P-gp specific. These findings indicated that nonionic surfactants including Cremophor EL and Tween 80 may be useful pharmaceutical excipients for inhibiting the function of P-gp, thereby increasing the intestinal absorption of various drugs, which are secreted by a P-gp-mediated efflux system in the intestine.

3-O-Methylglucose↗

PubMed1990

Identification and characterization of high-affinity Ca2(+)-ATPase associated with axonal plasma membranes of dog mesenteric nerves.

The microsomal fraction isolated from dog mesenteric nerve fibres was found to contain ATPase activity stimulated by micromolar concentrations of Ca ions. Such a high-affinity Ca2(+)-ATPase (hereafter referred to as HA Ca-ATPase) followed a Michaelis-Menten kinetics with Km for Ca ions of 0.4 microM and Vmax = 12.5 +/- 2.4 mumol Pi.mg-1h-1. The examination of the subcellular origin of HA Ca-ATPase revealed that this enzyme is associated with axonal plasma membranes as documented by its co-purification with several plasma membrane marker enzymes and with tetrodotoxin-sensitive 3H-saxitoxin binding. The addition of exogenous magnesium ions (Mg) resulted in a non-competitive inhibition of HA Ca-ATPase with Ki = 0.5 mM. The reaction velocity of HA Ca-ATPase was also inhibited by other divalent ions with the order of potency Mg greater than Mn greater than Zn greater than or equal to Co greater than Ni. In contrast to low affinity (high Km) Mg- and Ca-ATPase, the HA Ca-ATPase was insensitive to the inhibition by sodium azide (10 mM) and sodium fluoride (10 mM). Similarly, the specific activity of HA Ca-ATPase was unaffected by vanadate (100 microM) and N-ethylmaleinimide (100 microM). It is concluded that axonal plasma membranes of dog mesenteric nerves contain HA Ca-ATPase which seems to be unrelated to calcium-transporting Mg-dependent, Ca-stimulated ATPase.

Animals↗

PubMed1986

The thermoelastic effect in rigor muscle of the frog.

Small length changes were imposed on pairs of sartorius muscles from Rana temporaria and Rana pipiens in rigor and the mechanical and thermal responses studied. Rigor was induced by soaking the muscles overnight at 0 degrees C in a physiological salt solution containing 1.5 mM sodium azide and 0.4 mM sodium iodoacetate. Tension was measured at both the tibial and the pelvic ends of the preparation. Muscles were held at a steady tension of 20 to 76 kN m-2 and stretches or releases of 0.02 to 0.6 mm applied in pairs, with the initial change reversed several hundred milliseconds later. Single stretches resulted in heat absorption and releases in heat production by the preparation. Net heat production resulted from complete cycles of length changes larger than 0.1 mm, whether the initial change was a stretch or a release. The heat produced by the complete cycle was attributed to the movement of the muscles over the thermopile. It was proportional to the difference in tension between the tibial and pelvic ends of the preparation and increased with the size and speed of the length change. Half the heat produced by a complete cycle of length changes was subtracted from the thermal response recorded in the first half-cycle to obtain the reversible component of the response. The reversible component was linearly related to the tension change for all sizes and speeds of length change which were studied, with the heat:tension ratio ranging from -0.0093 to -0.0179 in eleven muscles (mean -0.0128 +/- 0.0009). The constancy of the heat:tension ratio in rigor muscles over a wide range of mechanical conditions indicates that the source of the thermal changes is the normal elasticity of the preparation. Since the size of the ratio is approximately the same as that measured in active muscles, the tension-dependent component of the thermal response to length changes applied to active muscles is probably also of elastic origin.

Animals↗

PubMed1977

Carnitine movement across muscle cell membranes. Studies in isolated rat muscle.

L-Carnitine uptake and exodus was studied in rat extensor digitorum longus muscle in vitro. A saturable transport process was observed, which had an apparent Km of 60 micron and V of 22 nmol/h per g tissue. Transport was inhibited by 2,4-dinitrophenol, sodium azide, anaerobiosis, ouabain, and sodium ion depletion. Analogs of L-carnitine containing a quarternary ammonium group were found to inhibit uptake (D-carnitine, Ki = 400 micron; gamma-butyrobetaine, Ki = 60 micron, choline chloride, Ki = 14 mM), while those not containing this functional group (gamma-aminobutyrate, D,L-beta-hydroxybutyrate) had no significant effect at concentrations 100 times the apparent Km of L-carnitine. Carnitine exodus from rat extensor digitorum longus muscle consisted of two phases. The rapid initial phase was attributed to leakage of L-carnitine from damaged muscle fibers, as it proceeded at nearly the same rat at 0 degrees and 37 degrees C, and then leveled off to a rate of near zero after 1 h of incubation in vitro. The quantitatively more important phase of exodus showed a latency of 1-2 h and then proceeded at a linear rate of 40-45 nmol/h per g tissue. The results of this study support the contention that L-carnitine is taken up by a carrier-mediated, active transport system in rat extensor digitorum longus muscle. Functionally, the transport system for uptake is distinct from the process by which carnitine is lost from this muscle.

Animals↗