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

Preincubation of HT29 cells with an alpha-2 adrenergic agonist resulted in a parallel rightward shift in the subsequent dose-response curve to 5-bromo-6-[2-imidazoline-2-yl-amino] quinoxaline (an alpha-2 adrenergic agonist) in inhibiting vasoactive intestinal peptide-stimulated cyclic AMP production. This rightward shift in the dose-response curve, which was concentration and time dependent, was interpreted as desensitization of the alpha-2 adrenergic receptor-mediated inhibition of cyclic AMP production. The fact that no decrease in efficacy was observed appears to result from a receptor reserve. Agonist preincubation effects on subsequent p-aminoclonidine (an alpha-2 adrenergic partial agonist) inhibition and partial irreversible inactivation of receptors confirmed the presence of an alpha-2 adrenergic receptor reserve in HT29 cells. Desensitization appeared to have a heterologous component since inhibition of vasoactive intestinal peptide-stimulated cyclic AMP production by somatostatin was also attenuated. We also assessed the effect of alpha-2 agonist preincubation on subsequent 5-bromo-6-[2-imidazoline-2-yl-amino] quinoxaline inhibition of parathyroid hormone-stimulated cyclic AMP production in OK cells. As with HT29 cells, agonist preincubation resulted in a concentration- and time-dependent shift in the dose-response curve. In both cell lines, long-term preincubation with an alpha-2 adrenergic agonist resulted in a 40% decrease in subsequent [3H]yohimbine binding, indicating down-regulation of the alpha-2 adrenergic receptor.
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PMID:Desensitization of the alpha-2 adrenergic receptor in HT29 and opossum kidney cell lines. 216 96

The specific melanotropin (MSH) binding sites of rat lacrimal glands were characterized with respect to anatomic distribution, peptide specificity and selectivity, and coupling to a biological response. Tissue distribution of MSH binding sites was determined by autoradiography following in situ binding of a radiolabeled, biologically active preparation of a superpotent alpha-MSH analog, [125I]-[Nle4,D-Phe7]-alpha-MSH ([125I]-NDP-MSH). Intense, specific (i.e., alpha-MSH-displaceable) [125I]-NDP-MSH binding was observed throughout lacrimal acinar tissue, but not in ducts or stroma. In freshly isolated lacrimal acinar cells, specific binding of [125I]-NDP-MSH was maximal within 30 min and rapidly reversible, with a dissociation half-time of about 15 min. A number of melanotropins [alpha-MSH, [N,O-diacetyl-Ser1]-alpha-MSH, [des-acetyl-Ser1]-alpha-MSH, beta-MSH, ACTH(1-24) and ACTH(1-39)] were recognized by these binding sites, as assessed by their inhibition of [125I]-NDP-MSH binding; NDP-MSH was the most potent (IC50 = 1.3 x 10(-9) M). In contrast, other peptides, including ACTH(4-10) and the nonmelanotropic peptides VIP, substance P, somatostatin, and ACTH(18-39) (CLIP), had no effects on tracer binding. In isolated lacrimal acinar cells, alpha-MSH and NDP-MSH stimulated intracellular cyclic AMP accumulation. We conclude that lacrimal acinar cells express functional receptors recognizing melanotropins, suggesting that the lacrimal gland may be a target for physiological regulation by endogenous melanotropins.
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PMID:Characterization of functional melanotropin receptors in lacrimal glands of the rat. 216 77

It has long been known that endogenous pyrogen, released as a result of injection of typhoid vaccine or in response to infection, produces fever and increases ACTH secretion. Recent studies have indicated that endogenous pyrogen is, at least in part, IL-1. This monokine has now been shown to activate the release of ACTH by a hypothalamic mechanism with release of CRF and possibly vasopressin, which stimulates the corticotrophs. There may also be a pituitary action to stimulate the release of ACTH directly. In our experiments we showed that IL-1 at low but not higher doses appears to act intrahypothalamically to stimulate GH and PRL release and to inhibit TSH release. In the meantime, another monokine, cachectin, was isolated and its structure determined. We have found that this monokine can act following its third ventricular injection to stimulate ACTH, PRL, and GH release and to inhibit TSH release, at least in part, by release of prostaglandins since indomethacin, an inhibitor of prostaglandin synthesis, produced a blockade of the responses except for those of ACTH. This peptide also has highly potent effects to alter pituitary hormone release by direct action on the pituitary to stimulate ACTH, GH, and TSH and to a slight extent PRL release. These actions appear to involve prostaglandins since indomethacin blocks all of the effects except for the effect on ACTH secretion. This monokine also produces a dose-related lowering of anterior pituitary cyclic AMP levels. When the monokine was incubated along with somatostatin, the lowering of cyclic AMP was reversed, and a potent PRL-releasing effect of the monokine was visible. We have begun studies with a third monokine, gamma interferon, which indicate that it stimulates ACTH release but suppresses plasma GH and TSH levels by a hypothalamic action. It is apparent that these various monokines have powerful effects to alter hypothalamic-pituitary function and that they probably mediate most of the effects of infections on the release of anterior pituitary hormones.
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PMID:Role of monokines in control of anterior pituitary hormone release. 223 30

Somatostatin and carbachol receptors are believed to be negatively coupled to adenylate cyclase in AtT-20 mouse pituitary tumor cells by an inhibitory guanine nucleotide-binding regulatory subunit. Activation of these receptors causes inhibition of cyclic AMP synthesis and adrenocorticotropin (ACTH) secretion stimulated by a variety of hormones. Secretion in response to several pharmacological agents, which do not increase AtT-20 cyclic AMP levels, is also antagonized by both somatostatin and carbachol. Inasmuch as ACTH secretion in response to all stimulants is dependent on extracellular calcium, the possibility that somatostatin and carbachol block calcium entry was investigated by observing the effects of these agents on the activity of the calcium channel activator, BAY-K-8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4- (2-trifluoromethylphenyl)-pyridine-5-carboxy-late] in AtT-20 cells. In first characterizing the effect of BAY-K-8644, it was noted that the channel agonist at 10(-10) to 10(-6) M itself rapidly increased basal ACTH secretion; higher concentrations (10(-4) M) reduced basal, (-)-isoproterenol, phorbol ester, 8-Br-cAMP and K+-stimulated secretion. BAY-K-8644 did not alter basal formation of cyclic AMP. The secretory response to BAY-K-8644 was dependent on extracellular calcium, and was inhibited by the calcium channel antagonist, nifedepine. When coapplied with (-)-isoproterenol, phorbol ester and 8-Br-cAMP, at a concentration which optimally stimulated ACTH secretion, BAY-K-8644 had an additive effect; the secretory responses to K+ (50 mM) or the calcium ionophore, A-23187, on the other hand, were potentiated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of adrenocorticotropin secretion from AtT-20 cells by the calcium channel activator, BAY-K-8644, and its inhibition by somatostatin and carbachol. 241 8

In the present study the effect of somatostatin on amylase secretion was determined using in vivo cannulation and isolated acini from rat pancreas. In vivo somatostatin-14 inhibited amylase secretion in basal state and that stimulated with CCK8 and acetylcholine. Somatostatin-14 and somatostatin-28 failed to inhibit amylase secretion from isolated acini in basal state and that stimulated with CCK8 and bethanechol. Somatostatin-14 did not increase 45Ca uptake or efflux of label from acini preloaded with 45Ca. Cellular cyclic AMP levels were not significantly increased. Somatostatin-14 did not alter the synthesis of proteins in vitro, as judged by incorporation of a mixture of fifteen 14C-labeled amino acids. Somatostatin-14 stimulated phosphoprotein phosphatase in higher doses, whereas no effect was observed at lower doses. Inhibition of secretion in vivo and lack of stimulation of amylase secretion in isolated acini suggest that the somatostatin effect in vivo is mediated by an indirect effect similar to other peptides, for example, opiates and neurotensin. Stimulation of phosphoprotein phosphatase suggests that somatostatin may bind to the acinar cells and affect functions other than secretion and synthesis of enzymes.
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PMID:Effect of somatostatin on amylase secretion from in vivo and in vitro rat pancreas. 242 87

The effects of a range of neuropeptides were investigated on the membrane potential of the Schwann cells of the giant nerve fibre of the tropical squid. Vasoactive intestinal peptide (VIP) produced a dose-dependent, long-lasting hyperpolarization of the Schwann-cell membrane potential. Among peptides structurally related to VIP, similar effects were produced by peptide histidine isoleucine (PHI) but not by secretin and glucagon. Substance P and somatostatin also hyperpolarized the Schwann-cell membrane potential but via receptor systems distinct from those activated by VIP. Methionine enkephalin ([Met]-enkephalin) blocked the actions of all the above peptides as well as the effects of DL-octopamine and carbachol. The actions of [Met]-enkephalin upon the VIP responses were antagonized by naloxone. VIP produces its effects on the Schwann-cell membrane potential via a receptor system that is independent from those described previously which mediate the effects of carbachol and DL-octopamine. However, VIP can potentiate the effects of the latter systems. The actions of VIP on the Schwann cell are unlikely to be mediated via changes in adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels and are insensitive to changes in the level of extracellular calcium in the superfusate. The actions of VIP are, however, potentiated in the presence of low concentrations of lithium ions suggesting that the VIP receptor may mediate its effects by inducing the hydrolysis of polyphosphatidylinositols in the Schwann-cell membrane. Evidence is presented for the existence of an endogenous VIP-like component in the normal hyperpolarizing action of giant-axon activity on the membrane potential of the Schwann cell.
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PMID:Peptidergic modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre. 243 97

The localization and distribution of catecholamines, selected neuropeptides, and the cyclic nucleotide second messengers has been determined in the superior cervical ganglion of the stroke-prone variant of the spontaneously hypertensive rat (SHR) and its normotensive Wistar-kyoto (WKY) control. Significant alteration in the frequency of occurrence of dopaminergic small intensely fluorescent cell clusters was seen in the stroke-prone variant of the SHR. The immunofluorescent localization of cyclic AMP (cAMP) and cyclic GMP (cGMP) were also changed in the stroke-prone variant, as was the immunofluorescent staining quantity of the neuropeptides somatostatin and substance P. The morphological pattern of staining for the various compounds in the normotensive control (WKY) was equivalent to the Sprague-Dawley rat strain. The implications of the altered neurochemistry in the superior cervical ganglion on the high blood pressure, and the predisposition for stroke in this strain are discussed.
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PMID:Neurochemical differences in the superior cervical ganglion of the spontaneously hypertensive rat stroke-prone variant. 244 7

Although relaxin acts at several abdominal sites and mammary tissue associated with pregnancy and parturition, the scope of target tissues and the signals conveying the relaxin message into the cell are poorly defined. We found that human relaxin rapidly elevates the cyclic AMP content of cultured rat anterior pituitary cells. This is a graded response (EC50 0.3 nM relaxin) that can be blocked by anti-relaxin antibodies or the hormones somatostatin and dopamine. Furthermore, other hormones with some sequence homology to relaxin, such as insulin and insulin-like growth factor-I, have no such action. We conclude that the anterior pituitary may be a target tissue for relaxin and that cyclic AMP may act as an intracellular messenger for relaxin in these cells.
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PMID:Human relaxin increases cyclic AMP levels in cultured anterior pituitary cells. 244 8

Under conditions in which vasoactive intestinal peptide (VIP) induces somatostatin release from cortical and diencephalic neuronal cultures, VIP causes large increases in intracellular cyclic AMP. Both the release of somatostatin and the increase in cyclic AMP elicited by VIP require exogenous calcium, can be blocked by cobalt ion, and can be qualitatively mimicked by depolarizating concentrations of exogenous potassium ion. Direct activation of adenylate cyclase by forskolin causes large increases in cyclic AMP content but does not induce somatostatin release. In the absence of VIP, the calcium ionophore, ionomycin, and the phorbol ester, phorbol 12-myristate-13-acetate, also stimulate somatostatin release. These results indicate that VIP-stimulation of cyclic AMP formation and VIP-stimulation of somatostatin release are calcium-dependent and that the two phenomena are dissociatable. Cyclic AMP formation is not a necessary condition for VIP-induced somatostatin release. Nucleotide formation may be a sufficient condition for release or, possibly in association with calcium influx, it may be an event unrelated to the release process.
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PMID:Adenylate cyclase activation is not sufficient to stimulate somatostatin release from dispersed cerebral cortical and diencephalic cells in glia-free cultures. 245 21

The effect of somatostatin (SS) on the pancreatic enzyme secretion was studied in a perfusion system using dispersed pancreatic rat acini in vitro. In addition the effect of SS on pancreatic secretion in vivo was also studied in conscious rats for comparison. In an in vitro study, 6 x 10(-7) M SS-14 caused no significant change in amylase release when added 20 min before stimulation by 10(-5) M carbamylcholine (Cch), 10(-6) M A23187, 5 x 10(-7) M secretin and 2 mM dibutyryl cyclic AMP. The addition of 6 x 10(-7) M SS-28 also caused no significant change in amylase release stimulated by 10(-5) M Cch. High performance liquid chromatographic examination indicated that no degradation of either SS-14 or SS-28 occurred after reaction with dispersed acini. In an in vivo study SS-14 caused marked inhibition of basal pancreatic secretion and stimulated pancreatic secretion by bile-pancreatic juice diversion. These results indicate that SS has no direct inhibitory action on rat pancreatic secretion, and that SS may inhibit the pancreatic secretion by indirect mechanisms.
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PMID:Effect of somatostatin on pancreatic enzyme secretion. 246 24


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