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)

TPA (12-O-tetradecanoylphorbol 13-acetate) is one of a class of compounds known as tumor promoters which perturb the inositol phosphate pathway in a number of cells. We have used TPA in a dispersed rat adenohypophysial cell system to probe the characteristics of growth hormone (GH) release. In this system we have found that the cells release GH in response to low concentrations of TPA: the EC50 was 0.23 +/- 0.05 nM (n = 6) and the maximal concentration was 5 nM. However, the maximal TPA-induced GH release was only 34 +/- 5% (n = 7) of the GH released by maximal growth hormone releasing factor (GRF) suggesting TPA releases a subpool of stored GH. Both somatostatin and insulin-like growth factor I inhibit GH release stimulated by TPA to the same extent as that stimulated by GRF, showing that the normal inhibitory control mechanism of release is not altered. Incubation in a low calcium medium that totally blocks GRF-stimulated GH release also inhibits TPA-stimulated GH release. The calcium channel blockers nifedipine and diltiazem both partly inhibit GRF- and TPA-stimulated GH release, showing some component of the calcium necessary for GH release arises from influx across the cell membrane.
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PMID:Characteristics of phorbol ester stimulated growth hormone release: inhibition by insulin-like growth factor I, somatostatin, and low calcium medium and comparison with growth hormone releasing factor. 289 38

Experiments were performed in vitro to examine the possible role of calcium and calmodulin in GRF-induced somatostatin (SRIF) release from the median eminence. Adult male rats were used as tissue donors. The median eminences were first prestimulated in 0.4 ml Krebs Ringer bicarbonate glucose buffer (pH 7.4) containing bacitracin at 37C in an atmosphere of 95% O2, 5% CO2 with constant shaking for 30 min. When calcium was omitted, this medium was used during the prestimulation and stimulation periods. After prestimulation, the medium was discarded and replaced by medium containing the different substances to be tested (GRF, EGTA, calcium channel blockers, and calmodulin inhibitors). The stimulation of SRIF release induced by 10(-10) M GRF was not inhibited by omission of extracellular calcium or when the remaining CA+2 was chelated with 10(-4) M EGTA. The calcium channel blockers, nifendipine and verapamil (10(-6) M), failed to alter the increase of SRIF release induced by rGRF. Three calmodulin inhibitors were employed to examine the possible influence of calmodulin on GRF-induced SRIF release. Trifluoperazine (10(-6) M), triflupromazine (10(-6) M) and penfluridol (10(-7) M) had an inhibitory effect on the stimulation of SRIF release induced by GRF and failed to alter resting release. Thus, GRF can evoke SRIF release independently of extraterminal Ca+2 concentration and Ca+2 influx into the nerve terminals, but the releasing process involves translocation of Ca+2 from intracellular stores. The inhibitory effect of the calmodulin inhibitors on GRF-induced SRIF release, suggests that the translocated Ca+2 must bind to calmodulin in order to release SRIF.
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PMID:Calmodulin dependence of somatostatin release stimulated by growth hormone-releasing factor. 289 60

Immunoreactive somatostatin (IRS) was identified in the male rat Harderian gland (HG) by radioimmunoassay. Tissue was extracted and a displacement curve performed; there were no significant differences between values obtained with serial dilutions of extracted tissue and those from purified somatostatin standard used in the radioimmunoassay. Basal values of HG-IRS were found to be in the nanomolar range (10.8 +/- 3.5 ng IRS/mg protein). Hypophysectomy did not change the HG-IRS but, in vivo growth hormone (GH) treatment led to a dramatic increase (6-7-fold) in the levels of IRS in the HG. Isoproterenol, a beta-adrenergic agonist, when administered in vivo significantly decreased the HG-IRS content. The effect of two different calcium channel blockers on the isoproterenol-induced decrease of HG-IRS was studied; no changes were observed with nifedipine but verapamil, injected one hour after isoproterenol administration, prevented the drop in HG-IRS levels. These data demonstrate the existence of IRS in a new location, the rat Harderian gland, and support a classical endocrine regulation for its tissue concentration.
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PMID:Identification of immunoreactive somatostatin in the rat harderian gland: regulation of its content by growth hormone, beta-adrenergic agonists and calcium channel blockers. 290 39

Parietal cell secretory function may be inhibited by three mechanisms. (1) Receptors for gastrin, histamine and acetylcholine are present on the canine parietal cell, and parietal cell function may be directly inhibited by specific antagonists for each of these receptors. (2) Receptor activation of parietal cell function is mediated by cyclic AMP-dependent (histamine) and calcium-dependent (cholinergic agents and gastrin) mechanisms. The antisecretory action of prostaglandins reflect interference with histamine activation of adenylate cyclase. The current generations of calcium channel blockers have only weak antisecretory actions in vivo and are unlikely to be useful in clinical practice. (3) A third mechanism of inhibition is blockade of H+/K(+)-ATPase by substituted benzimidazoles, such as omeprazole. Each of these three mechanism provides modalities of potential clinical usefulness for treating acid-peptic disease. Gastrin and acetylcholine receptors are present on other fundic cells, in addition to the parietal cell. These other cells include the somatostatin cell in the dog fundic mucosa and the histamine-containing enterochromaffin-like (ECL) cell present in the fundic mucosa of several species. The relative impact of these receptors on different cell types on the regulation of acid secretion remains uncertain, and is probably variable among different species. One gastrin receptor of considerable importance is the gastrin receptor that exerts a trophic effect on the ECL cell in the fundic mucosa. Sustained hypergastrinaemia in response to profound hypochlorhydria is associated with hyperplasia of this cell type; the elucidation of the conditions that promote this hyperplasia and the clinical consequences of this association are pressing challenges.
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PMID:Review: antisecretory drugs: cellular mechanisms of action. 297 19

The influence of membrane depolarization on somatostatin release from cerebral cortical neurons was examined. Fetal rat telencephalic cells, obtained by mechanoenzymatic dispersal, were maintained as organotypic monolayer cultures for 12 days before experimental studies. The immunoreactive somatostatin (IRS) released into the medium during a treatment epoch was compared to the amount released from the same cells during an immediately preceding control period. Potassium (60 mM) induced an increase in IRS secretion which was dependent on extracellular calcium concentration and could be prevented by the addition of the calcium channel blockers, cobalt or verapamil. Depolarization by veratridine, a sodium ionophore, also stimulated IRS release. The effect of veratridine was reversed by simultaneous exposure of the cells to either tetrodotoxin, a sodium channel blocker, or verapamil, a calcium channel blocker. These findings indicate that IRS release by cerebral cortical cells is stimulated by membrane depolarization and is dependent on both Na+ and Ca++ entry into the cells.
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PMID:Sodium- and calcium-dependent somatostatin release from dissociated cerebral cortical cells in culture. 612 71

We have developed a new short term in vitro system to examine hypothalamic somatostatin (SRIF) release. Hypothalamic cells were obtained from normal rats after trypsin or collagenase aided dispersion and released immuno-reactive (IR) SRIF which eluted in 3 molecular weight (MW) forms on gel chromatography. The smallest MW form, which constituted the major peak, co-eluted with synthetic cyclic 1-14 SRIF on gel and reverse phase high pressure liquid chromatography (HPLC). After 24 h in culture in medium containing heat inactivated fetal calf serum, cell viability was demonstrated by two techniques, (1) vital staining with trypan blue, and (2) incorporation of 32Pi into phospholipids. SRIF release was also studied at this time which was optimal in terms of responsivity of the cells to depolarizing stimuli. SRIF release increased in a time dependent manner, over 3 h. Membrane depolarization, induced either by potassium chloride 56 mM or ouabain (the Na+, K+-ATPase inhibitor) 10(-6) M or greater, markedly stimulated SRIF release. Incubation at 4 degrees C, or in the presence of EDTA 0.05 M or verapamil, the calcium channel blocker, 50 microM abolished these stimulatory effects. Glucose deprivation was induced by the addition of 2-deoxy-D-glucose (2-DG) to the experimental medium. 2-DG, at concentrations of up to 200 mg%, had no significant effect on SRIF release during incubation periods of up to 1 h.
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PMID:Somatostatin release from dispersed hypothalamic cells - effects of membrane depolarization, calcium and glucose deprivation. 613 93

Serotonin release from rabbit enterochromaffin cells located in the mucosal epithelium of the small intestine was studied in vitro. Serotonin release from both the serosal and mucosal sides of the small intestine was measured. The addition of muscarinic but not nicotinic cholinergic agonists to the serosal medium resulted in a large but transient increase in serotonin release from the serosal but not the mucosal side of the intestine. Mucosal addition of these agents was ineffective. Serotonin release stimulated by the cholinergic agonist carbachol appeared to be dependent upon influx of extracellular Ca++ for the following reasons: 1) depletion of serosal Ca++ inhibited carbachol-stimulated release; 2) carbachol-stimulated serotonin release was blocked by the inorganic calcium channel blockers Co++, Ni++, Cd++, La and Gd; and 3) serosal serotonin release was increased by the Ca++ ionophore, ionomycin, and by Ba++. The addition of 8-bromoadenosine cyclic AMP or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, to the serosal medium produced a sustained elevation of serosal serotonin release. 8-bromoadenosine-cyclic AMP-stimulated release was not blocked by depleting extracellular Ca++. Forskolin, a compound which stimulates adenylate cyclase, also stimulated serosal serotonin release. 8-bromoadenosine-cGMP had no effect on serotonin release. Somatostatin (10(-8)-10(-6) M) caused a dose-dependent inhibition of carbachol-stimulated serotonin release. Somatostatin (10(-6) M) only partially inhibited serotonin release stimulated by 8-bromoadenosine-cyclic AMP, 3-isobutyl-1-methylxanthine and forskolin and had no effect on release stimulated by Ba++. The results suggest potential roles for both calcium and cyclic nucleotides in the regulation of serotonin release.
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PMID:Regulation of serotonin release from rabbit intestinal enterochromaffin cells. 614 Mar 9

The effects of forskolin, an adenylate cyclase activator, were investigated on adrenocorticotropin (ACTH) secretion from AtT-20/ D16 -16 mouse pituitary tumor cells. Forskolin increased adenylate cyclase activity in these cells in the absence of added guanyl nucleotide, an effect blocked by somatostatin. Cyclic AMP synthesis and ACTH secretion increased in a concentration-dependent manner, not only in the clonal cells, but in primary cultures of rat anterior pituitary as well. Somatostatin inhibited cyclic AMP synthesis and ACTH secretion in response to forskolin. When forskolin was coapplied with corticotropin releasing factor, cyclic AMP synthesis was potentiated and ACTH secretion additive. The calcium channel blocker, nifedipine, inhibited forskolin, and 8-bromocyclic AMP stimulated ACTH secretion. These data suggest that ACTH secretion may be regulated at the molecular level by changes in cyclic AMP formation, which in turn regulate a calcium gating mechanism.
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PMID:Forskolin stimulates adenylate cyclase activity, cyclic AMP accumulation, and adrenocorticotropin secretion from mouse anterior pituitary tumor cells. 614 27

The identification of PHI (the 27-amino acid peptide (P) having an N-terminal histidine (H) and a C-terminal isoleucine amide (I] in median eminence suggested that PHI influences the secretory function of the anterior pituitary. The effects of PHI on ACTH release from clonal mouse pituitary corticotrophs were investigated. The secretory response to PHI was correlated with a prior increase in cyclic AMP accumulation. Both cyclic AMP synthesis and ACTH secretion were increased by PHI in a concentration-dependent manner. PHI was a less effective agonist of cyclic nucleotide synthesis and ACTH secretion than VIP. The secretory response to PHI was blocked by the calcium channel antagonist, nifedipine, and by dexamethasone. Somatostatin and oxotremorine blocked both PHI-stimulated cyclic AMP formation and ACTH secretion. The observation that VIP in high concentrations can elicit ACTH secretion from normal rat anterior pituitary suggested that a VIP-like substance may modulate ACTH secretion. However, the finding that PHI does not elicit ACTH release from primary cultures of dispersed anterior pituitary, coupled to its relatively lower potency compared to VIP, indicate that corticotrophs are not an important target for PHI.
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PMID:PHI stimulates ACTH release from pituitary tumor cell. 620 87

2-Deoxyglucose (2-DG) uptake is an index of regional glucose utilization which reflects predominantly activity in the axonal terminal of neuronal pathways. The present experiments showed that somatostatin elevated 2-DG uptake in rat cortex and hippocampus slices. Treatment with somatostatin-14 and somatostatin-28 markedly enhanced 2-DG uptake, whereas the amino-terminal fragment of somatostatin-28 did so only slightly. This effect appeared to be mediated by an interaction with somatostatin receptors because cyclo-somatostatin, a somatostatin antagonist, abolished the effect of somatostatin-14. The increase in 2-DG uptake caused by somatostatin-14 was blocked by the calcium channel antagonist, nifedipine, but not by tetrodotoxin, suggesting that the action of somatostatin does not require the initiation of impulse activity, somatostatin enhanced the KCl-induced release of acetylcholine, suggesting that a cholinergic mechanism is involved in the somatostatin-induced cellular responses. We therefore examined whether acetylcholine receptor antagonists block the somatostatin-induced increase in 2-DG uptake. Neither muscarinic nor nicotinic receptor antagonists affected the somatostatin-14-induced response. The present results suggest that somatostatin has a stimulatory effect on energy metabolism and that this effect is independent of acetylcholine receptor mechanism.
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PMID:Facilitation of 2-deoxyglucose uptake in rat cortex and hippocampus slices by somatostatin is independent of cholinergic activity. 809 64


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