Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing the extracellular K+ concentration to 71 mM causes a phasic release of growth hormone and efflux of 45Ca from perifused bovine pituitary cells. Verapamil (20 micron) partially inhibits the initial phase of growth hormone release and 45Ca efflux and completely inhibits the second phase. Somatostatin (1 microgram/ml) partially inhibits both phases of growth hormone release but does not modify 5+-induced 45Ca efflux. Incubation of pituitary cells in 71 mM K+ increases 45Ca incorporation; verapamil (20 micron) completely prevents, and somatostatin (1 microgram/ml) partially inhibits, the K+-induced increase in 45Ca incorporation. The results suggest that 71 mM K+ increases both calcium entry into the cells and calcium redistribution within them, and that verapamil only inhibits the K+-induced calcium entry. Somatostatin may inhibit calcium entry into tissue stores.
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PMID:Effects of somatostatin and verapamil on growth hormone release and 45Ca fluxes. 62 36

The study investigated the effects of metformin and phenformin, at "therapeutic" concentrations, on the pancreatic A-, B- and D- cell response to glucose using the isolated perfused rat pancreas model. Changes in the rate of pancreatic lactate output after these biguanides were also evaluated. Metformin--at 1.5 micrograms/ml--and phenformin--at 100 ng/ml--were separately infused both at 160 mg/dl and 300 mg/dl glucose levels. Neither metformin nor phenformin affected glucagon or somatostatin secretion during these two metabolic stimuli with glucose, nor did they significantly influence insulin response to the lower glucose stimulus. Both metformin and phenformin enhanced insulin response to 300 mg/dl glucose infusion and increased the second phase of the B-cell secretory profile but only phenformin significantly enhanced the pancreatic lactate output rate during the 300 mg/dl glucose infusion. Infusion with dichloroacetate (a stimulator of the mitochondrial pyruvate oxidation) or with verapamil (a calcium antagonist) alone did not modify the insulin response to high glucose concentrations. During metformin infusion dichloroacetate neither modified metformin's effects on B-cell response to high glucose nor did it affect the pancreatic lactate output rate. On the other hand dichloroacetate opposed phenformin's effects on the B-cell response to high glucose and reversed the rise in the pancreatic lactate output rate. Verapamil inhibited the effect of metformin on the B-cell response to high glucose but failed to affect phenformin's influence on high-glucose induced insulin release. These data suggest both metformin and phenformin potentiate--at least in rats--the late phase of insulin secretory response to high glucose. However metformin seems to influence pancreatic B-cell activity mainly by facilitating the trans-membrane calcium ion influx responsible for the second phase of insulin release. Phenformin's influence seems indirect since it increases pancreatic lactate production which mediates the enhanced B-cell response to glucose.
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PMID:Do metformin and phenformin potentiate differently B-cell response to high glucose? An in vitro study on isolated rat pancreas. 167 60

Primary cultures of rat hepatocytes were used for assaying several drugs not previously known for inhibiting the transport of phalloidin. In order to have 50% inhibition (IC50) of the entrance of a tritiated phallotoxin derivative ([3H]demethylphalloin, 1 microM) from the medium into the cells the following concentrations (microM) of the various inhibitors were determined: cyclolinopeptide (0.5), Nocloprost (5.0), Nileprost (7.0), beta-estradiol (42), Verapamil (70). For comparison, the corresponding IC50 values of some known antagonists of phalloidin toxicity were determined by the same method. Moreover, we studied several natural and synthetic phallotoxins and alpha-amanitin for their ability to displace [3H]demethylphalloin from the transporting system. Lineweaver-Burk plots made it obvious that two groups of inhibitors exist. Competitive inhibitors are, for example, antamanide, beta-estradiol, silybin, Nileprost, taurocholate, and the cyclic somatostatin analog cyclo[Phe-Thr-Lys-Trp-Phe-D-Pro], whereas Verapamil and monensin inhibit phallotoxin uptake in a non-competitive way. Considering the very different chemical features of the competitive inhibitors, we tentatively conclude that the phallotoxin transport system selects compounds not on the basis of their chemical features, but rather their physical properties. The physical properties of a typical substrate are low molecular mass, lipophilic nature, and, possibly the presence of rigid ring structures. Negative charges accelerate the transport of a substrate, while positive charges have the opposite effect. The phalloidin-transporting system may represent part of a hepatic equipment which clears portal blood from, for example, bile acids, lipophilic hormones, or xenobiotics. By chance, the transporting system incorporates phallotoxins into the hepatocytes leading to the death of these cells.
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PMID:Characterization of a transporting system in rat hepatocytes. Studies with competitive and non-competitive inhibitors of phalloidin transport. 287 38

The role of calcium (Ca2+) in bombesin (BBS)-stimulated release of gastrin and somatostatin-like immunoreactivity (SLI) was examined in isolated perfused rat stomachs obtained from male rats fasted overnight. The stomachs were perfused via the celiac artery. BBS (1 nM) was perfused alone for 10 min or in combination with various Ca2+ antagonists, including 1) different doses of divalent cationic Ca2+ chelator (EGTA), 2) Ca2+ channel blockers (nifedipine, verapamil), and 3) calmodulin (Ca2+ binding protein) antagonist [trifluoperazine (TFP)]. The effluent was collected for measurement of gastrin and SLI. EGTA at doses of 2 or 5 mM blocked the BBS-mediated release of both gastrin and SLI. After removal of a low dose of EGTA from the perfusate, the release of both gastrin and SLI rebounded. On removal of a high dose of EGTA, however, SLI release remained depressed, but gastrin rebounded even more significantly. In the absence of BBS, the rebound of gastrin release was less dramatic, indicating that reexposure to Ca2+ partially contributed to the rebound phenomenon. Nifedipine (0.1-10 microM) markedly decreased BBS-stimulated release of gastrin and SLI in a dose-dependent fashion; the inhibitory effect of nifedipine on SLI release was significantly stronger than on gastrin release. Verapamil (10 microM) depressed BBS-induced SLI release but not gastrin release. TFP (50 or 100 microM) also resulted in inhibition of bombesin-elicited release of gastrin and SLI in a dose-related manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of Ca2+ in bombesin-stimulated release of gastrin and somatostatin from isolated perfused rat stomach. 290 76

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.
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PMID:Studies on the mechanism of salicylate-induced increase of insulin secretion in man. 290 99

1. Growth hormone secretion, exchangeable cellular sodium and calcium concentrations measured by 22Na and 45Ca incorporation, and efflux of 45Ca were studied in dispersed bovine anterior pituitary cells. 2. Addition of veratridine (100 microM), an activator of sodium channels, increased exchangeable sodium and calcium concentrations in the cells, the efflux of 45Ca from prelabelled cells, and caused a biphasic stimulation of the rate of growth hormone secretion. Secretion of growth hormone was not stimulated when the extracellular calcium was decreased below 0.1 mM. 3. The increases in growth hormone secretion, exchangeable calcium concentration and 45Ca efflux from prelabelled cells caused by veratridine were abolished by addition of the calcium antagonist verapamil (20 microM). Verapamil also reduced the rise in exchangeable sodium caused by veratridine and increased the resting exchangeable sodium concentrations. 4. The peptide somatostatin (1 micrograms/ml) prevented veratridine-stimulated growth hormone secretion but did not inhibit the increases in exchangeable sodium and calcium caused by veratridine. The peptide itself elicited a transient increase in 45Ca efflux and subsequently partially inhibited veratridine-stimulated 45Ca efflux. 5. The data suggest that anterior pituitary cells possess voltage-sensitive sodium channels. Activation of these channels by veratridine may lead to depolarization and increased entry of calcium via potential-dependent calcium channels, which contributes to a rise in cytoplasmic calcium concentration and the subsequent stimulation of growth hormone secretion. We conclude that the calcium antagonist verapamil may also interact with sodium channels, and that the peptide somatostatin may act on growth-hormone-secreting cells either to prevent the rise in cytoplasmic calcium by hyperpolarizing the cells or to decrease the affinity of a population of calcium binding sites in the cells.
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PMID:Inhibition by somatostatin of bovine growth hormone secretion following sodium channel activation. 611 62

The effect of phorbol diester tumour promoters on the release of growth hormone (GH) and prolactin (Prl) was studied in rat pituitary cells cultured in monolayer. 12-O-tetradecanoyl phorbol-13-acetate (TPA), the most potent phorbol ester, stimulated GH accumulation in the cultured medium in a dose-dependent manner. TPA also stimulated Prl accumulation. A time course study indicated that TPA mainly stimulates release of GH. The maximal stimulation of GH release by TPA (100 ng/ml) was 3-4-fold over control. Phorbol-12,13-dibutyrate (PDB), another tumour-promoting phorbol ester, stimulated GH release to an extent similar to that of TPA, while a biologically inactive compound, phorbol-12,13-diacetate (PDA), had no effect. TPA-stimulated GH release was not affected by the presence of indomethacin, an inhibitor of prostaglandin (PG) synthesis, indicating that PG is not involved in the process of TPA-stimulated GH release. Co++, a competitive antagonist of Ca++, at 2.0 mM completely suppressed the GH release induced by TPA, and this inhibition was partially reversed by the addition of 2.0 mM Ca++. Verapamil, a Ca++ channel blocker, reduced TPA-stimulated GH release, and trifluoperazine, an inhibitor of Ca-calmodulin formation, had a similar effect. Somatostatin (SRIF) also inhibited the GH release by TPA. These observations are compatible with the idea that Ca++ may be involved in the process of TPA-stimulated GH release. Since TPA has been reported to activate a Ca++- and phospholipid-dependent protein kinase (protein kinase C), it is possible that TPA stimulate GH release by activating the enzyme. Further studies are required to clarify this point.
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PMID:Effect of phorbol esters on the release of growth hormone and prolactin from rat pituitary cells cultured in monolayer. 614 63

The stimulation of GH secretion from the anterior pituitary by synthetic GRF (hpGRF) is associated with a rapid increase in cAMP production. Within 5 min of the addition of 1 nM hpGRF to cultured rat anterior pituitary cells, intracellular cAMP levels are elevated 6-fold, with a maximal response being observed at 30 min. cAMP accumulation in the extracellular medium is also enhanced by this peptide. Comparison of the two cellular responses (GH secretion and cAMP formation) at various concentrations of hpGRF indicates that 10 times more hpGRF is required to obtain half-maximal stimulation of cAMP production than for GH secretion. Somatostatin totally blocks hpGRF-stimulated GH release, but only partially attenuates cAMP production in the presence or absence of a phosphodiesterase inhibitor. Verapamil also inhibits GH release in response to hpGRF, but, unlike somatostatin, this effect is not associated with an attenuation of cAMP production. In fact, intracellular cAMP levels are slightly augmented in the presence of verapamil, indicating that Ca2+ is required for hormone release but not for the activation of adenylate cyclase. Consistent with this is the observation that the release of GH due to 8-bromo-cAMP is also blocked by verapamil. A requirement for Ca2+ is further indicated by the inhibitory effects of CoCl2 and CdCl2 on both basal and hpGRF-stimulated GH release. These results suggest that cAMP may play a role as an intracellular mediator of GRF action in somatotrophs and that Ca2+ is required for the release process. Somatostatin may exert its inhibitory effects on GH secretion either by interfering with cAMP production or by an action on the secretory process subsequent to cAMP production.
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PMID:Stimulation of adenosine 3',5'-monophosphate production by growth hormone-releasing factor and its inhibition by somatostatin in anterior pituitary cells in vitro. 619 79

To study the interaction between the phospholipase C activation and the insulin secretion, isolated pancreatic islets were stimulated with glucose and the sulfated cholecystokinin octapeptide (CCK). To discriminate between intracellular mechanisms, experiments with agents inhibiting adenylyl cyclase and calcium-channels like somatostatin and verapamil, were performed. The phospholipase C activity, i.e. the accumulation of inositol phosphates, was increased by CCK (100 nmol l-1) at 3.3 mmol l-1 glucose. This effect of CCK did not require extracellular Ca2+, was not inhibited by somatostatin (100 nmol l-1), and no concomitant increase in the insulin secretion was observed. Both the phospholipase C activity and the insulin secretion increased in response to 12 mmol l-1 glucose. Somatostatin was able in some extent to inhibit these effects of glucose. At 12 mmol l-1 glucose, the phospholipase C activity and the insulin secretion were potentiated by CCK. CCK also counteracted the effect of somatostatin on the phospholipase C activity and the insulin secretion. Verapamil (2.5 umol l-1) more or less completely inhibited both the glucose-induced phospholipase C activity and the insulin secretion. Moreover, whereas the CCK-induced increase in the phospholipase C activity was unaffected, verapamil blocked the CCK-induced increase in the insulin secretion. We conclude that CCK directly activates phospholipase C, whereas glucose and somatostatin modulates phospholipase C via a Ca(2+)-dependent mechanism. CCK potentiates the insulin secretion by increased phospholipase C activity, but with a requirement of glucose at an apparent threshold level of Ca(2+)-influx.
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PMID:Cholecystokinin and somatostatin modulate the glucose-induced insulin secretion by different mechanisms in pancreatic islets. A study on phospholipase C activity and calcium requirement. 790 20

The current study was designed to determine whether dihydropyridine voltage-sensitive calcium channels were involved in the release of somatostatin from hypothalamic neurons, BAY K 8644 (?) a dihydropyridine with Ca(2+) channel agonistic properties elicited a dose-response release of somatostatin. The secretory responses observed either in the presence of 5 mM K(+) or 15 mM K(+) were similar; the EC(50) values were 9.6+/-0.05 nM and 9.3+/-0.08 nM respectively. Nifedipine, a dihydropyridine Ca(2+) channel antagonist and diltiazem, a benzothiazepine that also inhibits dihydropyridine sensitive Ca(2+) channels, decreased Bay K 8644-induced somatostatin release in a dose-dependent manner with IC(50)s of 0.39 +/- 0.05 ?M and 66+/-0.07 ?M. Verapamil, a phenylalkylamine tested at 50 ?M inhibited the evoked release by 65%. ?-conotoxin at concentrations ranging from 1 nM to 1 ?M, decreased BAY K 8644-stimulated somatostatin release in a dose-related manner, the lowest effective concentration being 1 nM. None of these drugs affected basal or K(+)-evoked release of somatostatin. These data suggest that in our experimental conditions, activation of dihydropyridine voltage sensitive-Ca(2+) channels induces somatostatin exocytosis although normally the Ca(2+) channels associated with stimulus-secretion coupling of somatostatin would not be dihydropyridine sensitive.
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PMID:Activation of dihydropyridine-sensitive calcium channels induces somatostatin release from hypothalamic neurons. Pharmacological characterization. 2050 13


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