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PubMed1987

Effects of cerebral ischemia on [3H]inositol lipids and [3H]inositol phosphates of gerbil brain and subcellular fractions.

Intracerebral injection of [3H]inositol into gerbil brain resulted in labeling of phosphoinositides and inositol-phosphates in various subcellular membrane fractions. Phosphatidylinositol (PI) comprised greater than 90% of the radioactivity of inositol lipids. However, the level of labeled poly-PI (with respect to PI) was higher in synaptosomes than in other membrane fractions. Ischemia induced in gerbils by ligation of the common carotid arteries resulted in a 30% decrease in labeled poly-PI in brain homogenates and this decrease was largely attributed to the poly-PI in synaptosomes (50% decrease). Among the inositol phosphates, the ischemia induction resulted in a decrease in labeling of inositol triphosphate (63%) and inositol biphosphate (38%), but labeling of inositol phosphate (IP) was increased by 59%. The results suggested a rapid turnover of the inositol phosphates in the gerbil brain. In general, changes in inositol lipids and inositol phosphates due to ischemia were attenuated after pretreatment with lithium (3 meq/kg) injected intraperitoneally 5 h prior to ligation. Surprisingly, lithium treatment alone did not cause an increase in IP labeling in the gerbil brain.

Animals↗

PubMed2001

Clinical pharmacokinetics of quetiapine: an atypical antipsychotic.

Quetiapine is a dibenzothiazepine derivative that has been evaluated for management of patients with the manifestations of psychotic disorders. In pharmacokinetic studies in humans, quetiapine was rapidly absorbed after oral administration, with median time to reach maximum observed plasma concentration ranging from 1 to 2 hours. The absolute bioavailability is unknown, but the relative bioavailability from orally administered tablets compared with a solution was nearly complete. Food has minimal effects on quetiapine absorption. The drug is approximately 83% bound to serum proteins. Single and multiple dose studies have demonstrated linear pharmacokinetics in the clinical dose range (up to 375mg twice daily). The drug is eliminated with a mean terminal half-life of approximately 7 hours. The primary route of elimination is through hepatic metabolism. In vitro studies show that quetiapine is predominantly metabolised by cytochrome P450 (CYP) 3A4. After administration of [14C]quetiapine, approximately 73% of the radioactivity was excreted in the urine and 21% in faeces. Quetiapine accounted for less than 1% of the excreted radioactivity. 11 metabolites formed through hepatic oxidation have been identified. Two were found to be pharmacologically active, but they circulate in plasma at 2 to 12% of the concentration of quetiapine and are unlikely to contribute substantially to the pharmacological effects of the drug. The pharmacokinetics of quetiapine do not appear to be altered by cigarette smoking. Oral clearance declines with age, and was reduced in 2 of 8 patients with hepatic dysfunction but not in patients with renal impairment. Quetiapine has no effect on the in vitro activity of CYP1A2, 2C9, 2C19, 2D6 and 3A4 at clinically relevant concentrations. The lack of effect of quetiapine on hepatic oxidation was confirmed in vivo by the lack of effect of quetiapine on antipyrine disposition. Quetiapine had no effect on serum lithium concentration. Phenytoin and thioridazine increase the clearance of quetiapine, and ketoconazole decreases clearance. No clinically significant effects of cimetidine, haloperidol, risperidone or imipramine on the pharmacokinetics of quetiapine were noted. Quetiapine dosage adjustment, therefore, may be necessary when coadministered with phenytoin, thioridazine or other potent CYP3A4 inducers or inhibitors. The relationship between the therapeutic effects and the plasma concentrations of quetiapine has been investigated in a multicentre clinical trial. There was no statistically significant association between trough plasma quetiapine concentration and clinical response as measured by traditional assessments of psychotic symptom severity. Subsequent clinical studies of the plasma concentration versus effect relationships for quetiapine may help to further define guidelines for dosage regimen design.

Adolescent↗

PubMed1985

Reconstitution of a bacterial Na+/H+ antiporter.

Membrane proteins from alkalophilic Bacillus firmus RAB were extracted with octylglucoside, reconstituted into liposomes made from alkalophile lipids. The proteoliposomes were loaded with 22Na+. Imposition of a valinomycin-mediated potassium diffusion potential, positive out, resulted in very rapid efflux of radioactive Na+ against its electrochemical gradient. That the Na+ efflux was mediated by the electrogenic Na+/H+ antiporter is indicated by the following characteristics that had been established for the porter in previous studies: dependence upon an electrical potential; pH sensitivity, with activity dependent upon an alkaline pH; inhibition by Li+; and an apparent concentration dependence upon Na+ that correlated well with measurements in cells and membrane vesicles.

Antiporters↗

PubMed2001

Study on the variation of indoor gamma radiation in the Dhaka district.

Monthly indoor gamma dose rates in 15 houses in the Dhaka district were measured for a period of a year using lithium fluoride (LiF) thermoluminescence dosemeters (TLD-100). The indoor gamma dose rate was found to vary between residences and with the age of buildings. A statistical analysis between indoor gamma dose rate and meteorological parameters, namely, teperature, rain fall, relative hamidity and atmospheric pressure was performed. The correlation between the measured gamma dose rate and meteorological parameters indicates that meteorological parameters influence the indoor gamma dose rate. It is proposed, however, that the ventilation rates of the houses should be considered.

Air Pollution, Indoor↗

PubMed1991

The synthesis of no-carrier-added DL-4-[18F]fluorodeprenyl via the nucleophilic aromatic substitution reaction.

No-carrier-added DL-alpha-methyl-beta-4-[18F]fluorophenyl-N-methyl-N-propynylethylamin e (DL-4-[18F]fluorodeprenyl) was synthesized via the following 3-step procedure: (1) nucleophilic aromatic substitution by [18F]fluoride on 4-nitrobenzaldehyde to produce 4-[18F]fluorobenzaldehyde (yield 65%); (2) the reaction of 4-[18F]fluorobenzaldehyde with (1-chloro-1-(trimethylsilyl)ethyl)lithium followed by hydrolysis to give 4-[18F]fluorophenylacetone (yield 50%); and (3) reductive alkylation of 4-[18F]fluorophenylacetone with N-methyl-propynylamine in the presence of NaBH3CN (yield 35%) followed by HPLC purification to give a racemic mixture of 4-[18F]fluorodeprenyl. The overall yield was 11% (EOB corrected), the synthesis time was 90 min and the specific activity greater than 0.57 Ci/mumol (end of synthesis). This synthesis approach, the conversion of an aromatic aldehyde to a homologous methyl ketone, extends the flexibility of the nucleophilic aromatic substitution reaction by applying it to the synthesis of radiotracers which do not bear electron-withdrawing activating groups on the aromatic ring. The tissue distribution of DL-4-[18F]fluorodeprenyl in mice at 1, 10 and 60 min was also measured and showed that metabolic defluorination was not significant. Clearance of radioactivity from brain after injection of DL-4-[18F]fluorodeprenyl was more rapid than that previously observed for [11C]L-deprenyl.

Animals↗

PubMed1978

Sodium concentrations affect metabolite uptake and cellular metabolism.

Rates of uptake of glucose (measured with 3H-2-deoxy-d-glucose), galactose, and leucine after exposure of chick embryo cells to increasing concentrations of Na+ over the range 100 to 200 mM. Uptake of nucleosides was unaffected by [Na+] over this range. Prior exposure of cells was required for the [Na+] effect on uptake. Changes were measureable within two hours after changing [Na+], and although the capacity for deoxyglucose uptake remained constant thereafter, the capacity for leucine uptake continued to change during the next few hours. Inhibition of protein synthesis by cycloheximide, or of RNA synthesis by Actinomycin D, failed to prevent these uptake changes. Analysis of the kinetics of uptake showed that only the Km for uptake of deoxyglucose or leucine was affected by [Na+]; the maximum V for each compound remained the same. Effects of [Na+]; could be distinguished from the increased capacity for glucose uptake induced by glucose starvation. Incorporation of both radioactive uridine into RNA, and radioactive thymidine into DNA, were affected by [Na+[, but the differences were not correlated with uptake of other metoblites. No differences in countable mitoses were apparent, although the growth of chick embryo cells in increased slightly with increasing [Na+]. Changes in uptake due to differing [Na+] also were observed in mammalian (rat NRK) cells. However, no effects of [Na+] on rates of cell growth or saturation density were observed with these cells.

Animals↗

PubMed1993

Mechanism of Na+/H+ exchange by Escherichia coli NhaA in reconstituted proteoliposomes.

Purified NhaA, a Na+/H+ antiporter from Escherichia coli, reconstituted into proteoliposomes was used to study partial reactions catalyzed by this protein. Homologous Na+/Na+ exchange as well as Na+/Li+ exchange via NhaA were detected by monitoring the effects of external Li+ and Na+ ions on the delta pH-driven sodium uptake into NH4 Cl-loaded vesicles. Furthermore, a sodium counterflow reaction was demonstrated in proteoliposomes preloaded with non-radioactive Na+ and placed into the experimental buffer containing low amounts of 22Na+ under experimental conditions when both components of protonmotive force generated by the antiporter. delta psi and delta pH, were dissipated by corresponding ionophores. The apparent Km for sodium counterflow is 1.1 mM, and Vmax is 80 mumol/min/mg of protein. External Na+ accelerates the downhill efflux of 22Na+ suggesting that the translocation of the Na(+)-loaded form of the carrier is faster than the rest of the catalytic cycle.

Antiporters↗

PubMed1986

Stimulation of phosphoinositide hydrolysis by oxytocin and the mechanism by which oxytocin controls prostaglandin synthesis in the ovine endometrium.

Slices of caruncular endometrium from steroid-treated ovariectomized sheep were incubated with myo-[2-3H]inositol to label tissue phosphatidylinositol. Effects of oxytocin were determined on the rate of incorporation of radioactivity into phosphatidylinositol and on the hydrolysis of phosphoinositides to inositol phosphates and diacylglycerol. Incorporation of radioactivity into phosphatidylinositol was linear during 2 h incubations; 10(-7) M (100 nM)-oxytocin caused a 2.8-fold increase in the rate of incorporation. In the presence of Li+, addition of 10(-7) M-oxytocin to slices in which phosphatidylinositol was pre-labelled caused mean increase of 40-fold in the incorporation of radioactivity into inositol mono-, bis- and tris-phosphates. Inositol 1,3,4-trisphosphate was quantitatively the major trisphosphate formed. The action of oxytocin on phosphoinositide hydrolysis was dose- and time-dependent, occurring at concentrations within the range observed in plasma during episodes of secretion in vivo, and with a time course comparable with that of the action of oxytocin on uterine prostaglandin production. The effect of oxytocin on incorporation of radioactivity into inositol phosphates was not affected by inhibitors of prostaglandin synthesis. Diacylglycerol 1- and 2-lipases in caruncular endometrium converted up to 72% of added 2-[3H]arachidonyldiacylglycerol into [3H]arachidonic acid during 30 min incubations at pH 7.0. Caruncular endometrium contained 1.49 mumol of phosphatidylinositol/g, representing approx. 0.2 mumol/g of phosphatidylinositol arachidonic acid. It is proposed that the stimulation of endometrial prostaglandin synthesis by oxytocin is accounted for by increased hydrolysis of phosphoinositides to diacylglycerol and inositol phosphates with subsequent release of arachidonic acid from diacylglycerol.

Animals↗

PubMed1991

Inositol cycling and phosphoinositide metabolism in rat pancreatic islets.

The effects of extracellular inositol and LiCl on intra-islet inositol cycling were investigated in isolated rat islets. Islets were cultured for 7 days in inositol-free RPMI 1640 containing 11.1 mM glucose and labeled with 3.7 MBq myo-[2-3H] inositol for the final 3 days. The labeled islets were then perifused under various conditions. There was a persistent increase in [3H] efflux from labeled islets stimulated with 16.7 mM glucose for 60 min. Addition of 5 mM inositol resulted in marked release of [3H] from islets and a decrease in radioactive inositol-lipid. When islets were perifused with 5 mM LiCl, the glucose-induced efflux of [3H] was greatly inhibited. The inhibitory effect of LiCl on [3H] efflux was partially corrected by the addition of 5 mM inositol. A prominent effect of LiCl was an increase in inositol monophosphate, indicating increased phospholipase C activity. This was detected within 5 min after glucose stimulation. The present data suggest that there is always very active intra-islet inositol cycling and that glucose can augument inositol-lipid metabolism.

Animals↗

PubMed1969

Studies on a nucleoprotein prepared from rat liver polysomes by digestion with T1 ribonuclease.

1. Treatment of rat liver polysomes in a buffer containing 2.5mm-magnesium chloride with T(1) ribonuclease at a concentration of 330units/ml. of reaction medium at 37 degrees for 2hr. leads to the production of an insoluble nucleoprotein. 2. On the bases of analysis for protein and RNA and of u.v.-absorption spectra the nucleoprotein appears to have lost approx. 60% of the structural RNA originally present in the ribosome. Degradation of (3)H-labelled polysomes (structural RNA labelled with orotic acid) with T(1) ribonuclease leads to nucleoprotein preparations retaining approx. 30% of the radioactivity originally present in the polysomes. By means of sucrose-density-gradient centrifugation it is shown that the nucleoprotein preparations are free of single 73s ribosomes and ribosomal subunits. No evidence for the presence of 28s and 18s structural RNA was obtained on examination of extracted nucleoprotein-particle RNA by means of sucrose-density-gradient centrifugation. 3. Digestion of washed polysomes carrying (14)C-labelled nascent peptide chains with T(1) ribonuclease gives a nucleoprotein particle that retains approx. 70% of the original labelled chains. Treatment of labelled nucleoprotein particles with 1mm-puromycin in the absence of transfer factors releases 20% of the labelled chains. Addition of GTP (0.48mumole) increases this release to 37%. 4. Treatment of nucleoprotein particles carrying (14)C-labelled peptide chains with either EDTA (50mm) or ammonium chloride (0.5m) brings about a small release of labelled material (approx. 15%). 5. Disruption of nucleoprotein particles carrying (14)C-labelled peptide chains with either sodium dodecyl sulphate or 2m-lithium chloride, followed by addition of transfer RNA as marker and chromatography on Sephadex G-200, show in both cases that considerable amounts of labelled peptide material move well ahead of the added transfer RNA marker. Further, if nucleoprotein particles carrying labelled peptide chains are treated with 0.3m-potassium hydroxide at 20 degrees for 24 hr., neutralized to pH7.6, and then chromatographed on Sephadex G-200, the labelled peptide material moves much closer to the added transfer RNA marker. These results suggest that a proportion of the nascent (14)C-labelled peptides on the nucleoprotein are attached to transfer RNA or large fragments of transfer RNA. 6. [(3)H]Polyuridylic acid binds to nucleoprotein particles in 1mm-magnesium chloride. The rate of binding is rapid when measured at 20 degrees .

Ammonium Chloride↗

PubMed1976

Chromatin proteins from normal, vegetalized, and animalized sea urchin embryos.

The chemical composition of the chromatin, the fractional content of histones and nonhistone chromatin proteins (NHP), and the biosynthesis of these proteins in normal, vegetalized, and animalized embryos of the sea urchin Strongylocentrotus droebachiensis at the blastula, mesenchyme blastula, and gastrula stages have been studied. The amount of the NHP in the chromatin from normal and vegetalized embryos increases during early embryonic development while that in animalized embryos remains without change at the mesenchyme blastula stage and then decreases. During development the histone content in all three cases slightly decreases. Polyacrylamide gel electrophoresis reveals that both fractional composition of histones and their biosynthesis in normal, vegetalized, and animalized embryos display no differences. During development, however, some changes occur, so that the relative amount of histones F1 and F2a2 increases, F2b decreases, while F3 and F2a1 remains constant. Histone F1 at the blastula stage consists of two subfractions while at the gastrula stage it consists of three subfractions. The histone F2a1 consists of one and two, respectively. Histone F3 at all stages is made up of three subfractions; histone F2b is made up of two; and the histone F2a2 is electrophoretically homogeneous. Specific radioactivity of the arginine-rich histones F3 and F2a1 tends to increase during development, while that of moderately lysine-rich histones F2b and F2a2 does not change, and that of the lysine-rich histone F1 decreases. The NHP in normal, vegetalized, and animalized embryos at different developmental stages consist of 17 fractions that can be separated by isoelectrofocusing within the 4.5-8.8 pH range. Quantitative changes have been observed in the fractions focused at pH 4.5-6.1 during development and in normal and modified embryos at the gastrula stage.

Animals↗

PubMed2006

The effect of sodium chloride on the dissolution of calcium silicate hydrate gels.

The use of cement based materials will be widespread in the long-term management of radioactive materials in the United Kingdom. One of the applications could be the Nirex reference vault backfill (NRVB) as an engineered barrier within a deep geological repository. NRVB confers alkaline conditions, which would provide a robust chemical barrier through the control of the solubility of some key radionuclides, enhanced sorption and minimised corrosion of steel containers. An understanding of the dissolution of C-S-H gels in cement under the appropriate conditions (e.g., saline groundwaters) is necessary to demonstrate the expected evolution of the chemistry over time and to provide sufficient cement to buffer the porewater conditions for the required time. A programme of experimental work has been undertaken to investigate C-S-H gel dissolution behaviour in sodium chloride solutions and the effect of calcium/silicon ratio (C/S), temperature and cation type on this behaviour. Reductions in calcium concentration and pH values were observed with samples equilibrated at 45 degrees C compared to those prepared at 25 degrees C. The effect of salt cation type on salt-concentration dependence of the dissolution of C-S-H gels was investigated by the addition of lithium or potassium chloride in place of sodium chloride for gels with a C/S of 1.0 and 1.8. With a C/S of 1.0, similar increases in dissolved calcium concentration with increasing ionic strength were recorded for the different salts. However, at a C/S of 1.8, anomalously high calcium concentrations were observed in the presence of lithium.

Calcium Compounds↗

PubMed1988

3'-Deoxy-NAD+ as a substrate for poly(ADP-ribose)polymerase and the reaction mechanism of poly(ADP-ribose) elongation.

Adenyl-32P-Labeled 3'-deoxy-NAD+ was utilized as a substrate by pure DNA-dependent poly(ADP-ribose)polymerase (EC 2.4.2.30) from calf thymus in the automodification reaction with an apparent Km of 20 microM and a Vmax of 80 nmol/min/mg of protein. Analysis by lithium lauryl sulfate-polyacrylamide gel electrophoresis revealed a single 32P-labeled protein of 116-kDa which comigrated with automodified enzyme. Addition of increasing amounts of histone H1 up to a concentration of 15 micrograms/ml stimulated the synthesis of protein-bound polymers of 3'-deoxy-ADP-ribose. However, the average polymer size was equal to 2 in the presence and 4 in the absence of histone H1, respectively. The synthesis of protein-bound oligomers of 3'-deoxy-ADP-ribose was inhibited by the polymerase inhibitors benzamide, nicotinamide, thymidine, and NaCl. A pulse labeling of polymer synthesis with 40 microM [32P]3'-deoxy-NAD+ either in the presence or absence of 15 micrograms/ml of histone H1, followed by a chase with 1 mM [3H]NAD+, was used to determine the mechanism of poly(ADP-ribose) elongation. Following enzyme digestion of these polymers with phosphodiesterase, it was found that 52 and 24% of the total 32P radiolabel was associated with the 3'-deoxy-AMP termini of the polymers synthesized in the pulse reactions, in the presence or absence of histone H1, respectively. In contrast, less than 10% of the total radioactivity was associated with 3'-deoxy-AMP in the product of the chase reactions. These results are consistent with the conclusion that the initially attached residue of 3'-deoxy-ADP-ribose to either the polymerase or histone H1, is elongated by the "protein-distal" addition of ADP-ribose residues to the AMP terminus of the growing polymer chain.

Animals↗

PubMed2002

In vitro and in vivo characteristics of a human colon cancer cell line, SNU-C5N, expressing sodium-iodide symporter.

Rat NIS (rNIS) genes were transfected into a human colon cancer cell line (SNU-C5) by lipofection. The transfected cells (SNU-C5N) exhibited an increase 125I uptake to a level 10 times higher than the untransfected SNU-C5 cells. The addition of 300 microM DIDS, an anion channel blocker, to the culture media led to a 2.35 times increase of 125I uptake in the cells. For the first 10 minutes, up to 70% of the cellular radioactivity was released into the medium. In the biodistribution study using SNU-C5N-xenografted mice, the %ID/g of the SNU-C5N tumors at 1, 3, 6, and 12 h after the 125I injection were 4.43%, 1.09%, 1.05%, and 0.05%, respectively, which were significantly higher than those for the SNU-C5 tumors (P<0.05). In tumor imaging, the SNU-C5N-xenografted tumor was clearly visible. In this study, NIS lipofection is efficient for triggering significant iodide uptake by a nonthyroidal tumor. However, for an increased therapeutic effect, the key issue is iodide retention in the target tissue.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMedDate not supplied

Testing and parameterizing a conceptual solute transport model in saturated fractured tuff using sorbing and nonsorbing tracers in cross-hole tracer tests.

Two cross-hole tracer tests involving the simultaneous injection of two nonsorbing solute tracers with different diffusion coefficients (bromide and pentafluorobenzoate) and one weakly sorbing solute tracer (lithium ion) were conducted in two different intervals at the C-wells complex near the site of a potential high-level nuclear waste repository at Yucca Mountain, NV. The tests were conducted to (1) test a conceptual radionuclide transport model for saturated, fractured tuffs near Yucca Mountain and (2) obtain transport parameter estimates for predictive modeling of radionuclide transport. The differences between the responses of the two nonsorbing tracers and the sorbing tracer (when normalized to injection masses) were consistent with a dual-porosity transport system in which matrix diffusion was occurring. The concentration attenuation of the sorbing tracer relative to the nonsorbing tracers suggested that diffusion occurred primarily into matrix pores, not simply into stagnant water within the fractures. The K(d) values deduced from the lithium responses were generally larger than K(d) values measured in laboratory batch sorption tests using crushed C-wells cores. This result supports the use of laboratory-derived K(d) values for predicting sorbing species transport at the site, as the laboratory K(d) values would result in underprediction of sorption and hence conservative transport predictions. The tracer tests also provided estimates of effective flow porosity and longitudinal dispersivity at the site. The tests clearly demonstrated the advantages of using multiple tracers of different physical and chemical characteristics to distinguish between alternative conceptual transport models and to obtain transport parameter estimates that are better constrained than can be obtained using only a single tracer or using multiple nonsorbing tracers without a sorbing tracer.

Benzoates↗

PubMed1995

Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients.

Some evidence points towards a possible autoimmune role in the aetiology of schizophrenia. Experimental findings provide contradictory results regarding abnormalities in cytokine production in this disorder. In the present study we tested the production of cytokines in CSF and serum in 16 schizophrenic patients and 10 healthy controls (tumor necrosis factor alpha - TNF alpha; interleukins IL-1 beta, IL-2, IL-6, soluble IL-2 receptor). Cytokine levels were evaluated by radioactively-labeled antibodies (IL-1 beta, IL-2, IL-6), by enzyme-linked immunoassay (TNF) and by a sandwich enzyme immunoassay (soluble IL-2 receptor). No significant differences were found in either CSF fluid or serum levels of TNF and IL-2 or IL-6. Interleukin-1 beta was significantly decreased in patients' CSF and serum as compared to controls. Soluble interleukin-2 receptor levels were decreased in CSF of patients, but highly increased in their serum in comparison with controls. Changes in various cytokine levels in CSF fluid and serum of schizophrenic patients probably reflect interrelated process of growth, degeneration or neuroimmunological abnormalities, which may all play a role in the pathophysiology of schizophrenia. The present study supports evidence for change in immune activation, probably of peripheral origin, in schizophrenic patients.

Adult↗

PubMed1988

Hepatic inositol release upon hormonal stimulation of perfused rat liver.

A sustained increase in the hepatic release of 3H radioactivity was shown to occur upon hormonal stimulation of perfused rat liver 15-20 h after intraperitoneal injection of 100 microCi of myo-[2-3H]inositol. Hormone-released radioactive material was analysed by t.l.c. and was found to consist predominantly of [3H]inositol, without further metabolites. Vasopressin (14 nM), phenylephrine (1.7 microM), angiotensin II (15 nM), glucagon (0.5 nM) and dibutyryl cyclic AMP (5 microM) exert maximal effects on hepatic inositol efflux after 10-15 min of stimulation. Omission of Ca2+ from the perfusion medium abolishes the hormone-dependent inositol release. LiCl (10 mM) does not significantly affect the basal release of [3H]inositol, but suppresses vasopressin- and angiotensin-triggered inositol release. Inositol efflux induced by glucagon, dibutyryl cyclic AMP and phenylephrine, however, remains essentially unchanged by LiCl infusion. This establishes a further metabolic difference between these two groups of agonists in that stimuli that act through cyclic AMP produce a stimulated outflow of inositol, but apparently without a Li+-sensitive phosphatase being involved in the overall process.

Angiotensin II↗

PubMed1986

Stimulation, by vasopressin and other agonists, of inositol-lipid breakdown and inositol phosphate accumulation in WRK 1 cells.

WRK 1 cells were labelled to equilibrium with 2-myo-[3H]inositol and stimulated with vasopressin. Within 3 s of hormone stimulation there was a marked accumulation of 3H-labelled InsP2 and InsP3 (inositol bis- and tris-phosphate), but not of InsP (inositol monophosphate). There was an associated, and rapid, depletion of 3H-labelled PtdInsP and PtdInsP2 (phosphatidylinositol mono- and bis-phosphates), but not of PtdIns (phosphatidylinositol), in these cells. Some 4% of the radioactivity in the total inositol lipid pool of WRK 1 cells was recovered in InsP2 and InsP3 after 10 s stimulation with the hormone. The selectivity of the vasopressin receptors of WRK 1 cells for a variety of vasopressin agonists and antagonists revealed these to be of the V1a subtype. There was no receptor reserve for vasopressin-stimulated inositol phosphate accumulation in WRK 1 cells. The accumulation of inositol phosphates was enhanced in the presence of Li+ions. Half-maximal accumulation of InsP, InsP2 and InsP3 in vasopressin-stimulated cells was observed with 0.9, 3.0 and 3.6 mM-Li+ respectively. Bradykinin and 5-hydroxytryptamine also provoked inositol phosphate accumulation in WRK 1 cells. The effects of sub-optimal concentrations of bradykinin and vasopressin upon inositol phosphate accumulation were additive, but those of optimal concentrations of the hormones were not.

Animals↗