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)

Somatostatin analog SMS 201-995 causes a dose-related suppression of the release and/or action of several gastrointestinal hormones and impairs several anterior pituitary functions. Some patients with illness involving abnormal hormonal activity have responded to treatment with SMS 201-995, including resolution of severe secretory diarrhea. This study examined SMS 201-995 inhibition of Escherichia coli heat-stable enterotoxin STa (STa) effects and effects of the analog in the rabbit RITARD model with enterotoxigenic Escherichia coli. SMS 201-995 did not alter STa binding to its receptor on piglet brush border membranes. The analog, at concentrations of 0.1 micrograms/ml (0.1 microM) and 1 microgram/ml (1 microM) did not significantly alter STa activation of intestinal epithelial cell particulate guanylate cyclase. At maximal dosing the analog significantly reduced intestinal fluid secretion in suckling mice that was induced by either 8-bromo cyclic GMP or STa. In piglets, the analog reduced by 37-44% the amount of diarrhea induced by STa. However, even with maximal dosing, the piglets still had significant diarrhea, although of a lesser amount. In the rabbit RITARD model the drug failed to alter the severe diarrheal response seen when dosing the animals with enterotoxigenic Escherichia coli. Overall, SMS 201-995 had a significant but incomplete effect in reducing the STa effects seen in the various assays. Additionally, in the RITARD model the analog did not alter the clinical responses to various enterotoxigenic bacteria. SMS 201-995 should be useful as a probe into the mechanisms involved in intestinal fluid secretion, but a clinical role in enterotoxigenic gastrointestinal disease was not supported by this study.
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PMID:Effects of somatostatin analog SMS 201-995 on enterotoxigenic diarrhea. 168 50

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

The Mongolian gerbil, with its spontaneous epileptiform seizures, was chosen as an experimental model of human epilepsy. Neurochemical parameters possibly related to the seizure process were studied. In the immediate seizure process amino acid profiles of cortex, hippocampus, and striatum were not different in seizuring animals when compared to seizure-resistance controls. Of two peptides analyzed, only somatostatin appeared elevated in the cortex 2 hr postictal (143 fmol/mg protein; controls, 123 fmol/mg protein); neuropeptide Y was not affected. A follow up of the time course of cyclic AMP and cyclic GMP showed significant elevations of both substances as a consequence of seizures. Most prominent was a 5.5-fold increase in cyclic GMP in the cerebellum 30 sec after seizure onset.
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PMID:Biochemical events in spontaneous seizures in the Mongolian gerbil. 256 12

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.
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PMID:Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family. 257 21

Thymosin fraction 5 (TF5) is a partially purified extract of bovine thymus containing 40-60 peptides. In addition to its well documented immunopotentiating effects, TF5 reportedly modulates the secretion of some hypothalamic peptides and pituitary hormones. In this study, TF5 (10-100 micrograms/ml) stimulated PRL release from normal, MtTW15, and 7315a cells and GH release from normal and MtTW15 cells, but had no apparent effect on LH release. No changes in intracellular cAMP or cGMP levels could be correlated with these responses. Stimulation of PRL release from perifused normal anterior pituitary cells was rapid, sustained, and concentration related. Although it had no apparent effect on normal prelabeled anterior pituitary cells with respect to 45Ca2+ efflux, the calcium channel blocker D-600 inhibited TF5-mediated hormone release from these cells. Additive increases in TRH-stimulated PRL release and GRF-stimulated GH release by TF5 suggested independent mechanisms of action. Dopamine (500 nM) blocked TF5-stimulated PRL release, but somatostatin (10-100 nM) had no effect on TF5-stimulated PRL or GH release. TF5 failed to affect either basal or TRH-induced polyphosphoinositide hydrolysis. Perifused normal anterior pituitary cells prelabeled with [3H]arachidonate responded to TF5 treatment with a liberation of radioactive arachidonate and/or its metabolites. BW755c, an inhibitor of all known catabolic pathways of arachidonic acid, blocked the ability of TF5 to stimulate PRL and GH release. Reversed phase HPLC separation of TF5 into five fractions resulted in two fractions that exhibited hormone-releasing activity. These data suggest that TF5 stimulates pituitary hormone release through a mechanism different from that ascribed to TRH or GRF. The stimulus-secretion coupling mechanism involves neither polyphosphoinositide hydrolysis nor cAMP generation, but appears to be dependent on the generation of arachidonate metabolites.
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PMID:Thymosin fraction 5 stimulates prolactin and growth hormone release from anterior pituitary cells in vitro. 282 78

The influence of cyclic 3',5'-guanosine monophosphate (cGMP) on the lipolytic and antilipolytic (inhibition of glucagon-stimulated lipolysis) responses to GH (1 microgram/ml) was examined in chicken adipose tissue in vitro. Both 8-bromo-cGMP (0.1 mM) and sodium nitroprusside (1 mM) (a guanyl cyclase stimulator) completely inhibited the lipolytic effect of GH. A cGMP-lowering agent, LY83583 (10 microM), reversed the inhibitory effect of sodium nitroprusside on GH-stimulated lipolysis. Furthermore, the suppressive effects of insulin (100 ng/ml), insulin-like growth factor I (IGF-I) (100 ng/ml), or insulin-like growth factor II (IGF-II/MSA) (100 ng/ml), but not somatostatin (1 ng/ml), on GH-stimulated lipolysis were prevented by LY83583 addition. Neither 8-bromo-cGMP, sodium nitroprusside, nor LY83583 altered GH-induced inhibition of glucagon (1 ng/ml)-stimulated lipolysis. It is proposed that cGMP may mediate inhibitory control of GH-stimulated lipolysis by insulin, IGF-I, and IGF-II in chicken adipose tissue.
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PMID:Inhibition of growth hormone-induced lipolysis by 3',5'-guanosine monophosphate in chicken adipose tissue in vitro. 284 72

Somatostatin (SS) in 10(-9)-10(-7) M concentrations stimulated the lysis and inhibited the incorporation of IgG2a-coated 51Cr-labeled sheep red blood cell (SRBC) by rat peritoneal macrophages (PM). The intracellular killing capacity of PM remained unchanged. The enhancement of Fc receptor (R) activity and generation of active oxygen species were found to be responsible for the antibody-dependent cellular cytotoxicity (ADCC)-stimulating effect of SS. It was demonstrated that the stimulation of ADCC was abolished by the calmodulin inhibitor trifluoperazine (TFP), whereas it proved to be independent of the Ca2+ uptake. In addition, SS in the ADCC-stimulating concentrations diminished the intracellular cAMP generation and progressively increased the cGMP level. In higher (10(-6)-10(-7) M) concentrations, SS had a controversial effect on PM: it inhibited ADCC through the activation of both the adenylate cyclase and Ca2+ influx.
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PMID:The mechanism of antibody-dependent cellular cytotoxicity stimulation by somatostatin in rat peritoneal macrophages. 285 14

The effect of somatostatin on cyclic AMP-protein kinase system and lipid metabolism was studied in mouse brain. Subcutaneous injection of the peptide decreased the cyclic AMP and cyclic GMP levels (70% and 60% respectively) as well as protein kinase and triglyceride lipase activities (30%). Cyclic AMP binding protein activity was not affected. Experiments carried out with [14C]acetate as precursor of lipids seem to indicate that somatostatin blocks the fatty acid turnover. On the other hand, the general decrease of 32P incorporation into all phospholipids by somatostatin suggests that the peptide interferes with the precursor uptake into phospholipids. The findings reported here indicate that somatostatin has a role on brain metabolism and further add more data in support for its neuromodulating action.
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PMID:Somatostatin effects on the cyclic AMP system and lipid metabolism in mouse brain. 287 18

This study examined the effects of transmural nerve stimulation, acetylcholine, adrenoceptor agonists and several peptides on the contractility of strips of human gallbladder in vitro. Acetylcholine caused concentration-related contractions of the tissues and the sensitivity to acetylcholine was similar in gallbladders with mild and severe chronic cholecystitis. Noradrenaline and adrenaline relaxed gallbladder strips, probably via beta 2-adrenoceptor stimulation. Transmural nerve stimulation always caused contractions, but in the presence of atropine inhibitory responses were demonstrable and these were antagonized by propranolol. There was no evidence of non-adrenergic inhibitory neural responses. Of the peptides tested, only cholecystokinin octapeptide (CCK-OP), gastrin, pentagastrin, substance P and caerulein caused contractions. Responses to CCK-OP, gastrin and pentagastrin were antagonized by dibutyryl cyclic GMP. Hormones which had no effect upon human gallbladder strips included motilin, secretin, bombesin, neurotensin, glucagon, vasopressin, VIP and somatostatin. Considerable differences therefore exist between human tissues and those from experimental animals with respect to the direct actions of neural and hormonal stimuli on gallbladder contractility.
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PMID:Contractility of human gallbladder muscle in vitro. 297 88

Two cell culture systems were used for studies of neural functions in vitro. A neuronal hybrid cell line (neuroblastoma x glioma hybrid cells) and primary glial-rich cultures of newborn murine brain. The level of cyclic AMP in both systems is regulated by two groups of hormones, those that stimulate and those that inhibit formation of cyclic AMP. Among the inhibitory hormones active on the hybrid cells are opioids. Therefore the cells are being used in the elucidation of action of opioids. The list of stimulating and inhibitory hormones regulating the primary glial-rich cultures includes several peptide hormones such as the gastrointestinal peptides secretin and vasoactive intestinal peptide, the calcaemic hormones parathyrin and calcitonin, adrenocorticotropin and melanotropins, and somatostatin. Noradrenaline (via alpha- and beta-adrenergic receptors) and adenosine (via A1 and A2 receptors) inhibit and stimulate cyclic AMP synthesis in the primary glial-rich cultures. Bradykinin slowly hyperpolarizes the hybrid cells and elicits formation of cyclic GMP. Both responses desensitize rapidly. Substance P increases the permeability of hybrid cells for Na+, as measured by using 14C-guanidinium as substitute for Na+. Hybrid cells actively accumulate taurine, an amino acid that appears to fulfill important functions in the nervous system. The transport of taurine across the plasma membrane is highly specific for and strictly dependent on Na+. The pumped station hypothesis of taurine action in the nervous system views taurine gradient plus taurine carrier as a transport system for the elimination of sodium from neurons during phases of high neuronal activity.
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PMID:Cell culture as models for studying neural functions. 608 74


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