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)

Regulatory GTP-binding proteins (G proteins) are membrane-attached heterotrimers (alpha, beta, gamma) that mediate cellular responses to a wide variety of extracellular stimuli. They undergo a cycle of guanine-nucleotide exchange and GTP hydrolysis, during which they dissociate into alpha-subunit and beta gamma complex. The roles of G-protein alpha-subunits in these processes and for the specificity of signal transduction are largely established; the beta- and gamma-subunits are essential for receptor-induced G-protein activation and seem to be less diverse and less specific. Although the complementary DNAs for several beta-subunits have been cloned, isolated subunits have only been studied as beta gamma complexes. Functional differences have been ascribed to the gamma-subunit on the basis of extensive sequence similarity among beta-subunits and apparent heterogeneity in gamma-subunit sequences. Beta gamma complexes can interact directly or indirectly with different effectors. They seem to be interchangeable in their interaction with pertussis toxin-sensitive alpha-subunits, so we tested this by microinjecting antisense oligonucleotides into nuclei of a rat pituitary cell line to suppress the synthesis of individual beta-subunits selectively. Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels.
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PMID:Different beta-subunits determine G-protein interaction with transmembrane receptors. 132 98

Catecholamines acting through beta 1- and beta 2-adrenoceptors cause positive inotropic and chronotropic effects in the human heart. In recent years, however, evidence has accumulated that in the human heart also other receptor systems can affect heart rate and/or contractility. Positive inotropic effects can be mediated by receptor systems acting through accumulation of intracellular cAMP (Gs-protein coupled receptors such as 5-HT4-like, histamine H2, and vasoactive intestinal peptide) or by receptor systems acting independent of cAMP possibly through the phospholipase C/diacylglycerol/inositol-1,4,5-trisphosphate pathway (such as alpha 1-adrenergic, angiotensin II, and endothelin). In the non-failing human heart, however, activation of all these receptor systems induces only submaximal positive inotropic effects when compared with those caused by beta-adrenoceptor stimulation, indicating that in humans the cardiac beta-adrenoceptor-Gs-protein-adenylate cyclase pathway is the most powerful mechanism to increase heart rate and contractility. On the other hand, at least three receptor systems acting through inhibition of cAMP formation (Gi-protein coupled receptors) exist in the human heart: muscarinic M2-, adenosine A1-, and somatostatin-receptors. Activation of M2- and A1-receptors causes negative inotropic effects in the non-failing human heart: in atria activation of both receptors causes decreases in basal as well as in isoprenaline-stimulated force of contraction, but in ventricles only isoprenaline-stimulated force of contraction is depressed.
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PMID:Receptor systems in the non-failing human heart. 135 55

The purpose of the present study was to evaluate the effects of both intra-arterial and intravenous infusions of somatostatin, serotonin (5-hydroxytryptamine) and isoprenaline beta 1- + beta 2-adrenoceptor agonist) on gastric acid and pepsin secretion in conscious dogs with a gastric fistula. The drugs mentioned have been examined earlier for effects on gastric secretion in vivo during intravenous infusions and these effects could be hampered by the possible indirect mechanism of action as well as the different kinetics of metabolism. A catheter (vascular access port) allowed repeatedly gastric intra-arterial infusions. Somatostatin and serotonin possessed inhibitory effects on gastric acid and pepsin secretion and were without significant differences between the analyzed ways of administration. Intra-arterial infusion, isoprenaline possessed less potent inhibitory effects on gastric secretion: the effects were significant for pepsin secretion but were nonsignificant for acid secretion. The results suggest the mechanism of action of isoprenaline, somatostatin and sertonin to diverge, and for somatostatin and serotonin it was independent of the route of administration.
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PMID:Intra-arterial versus intravenous administration of gastric secretory inhibitors in conscious dogs. Effects of somatostatin, serotonin and isoprenaline on acid and pepsin secretion. 167 13

The effect of the selective beta 1-adrenergic blocking agent atenolol (50 or 100 mg, orally) on spontaneous and GH-releasing hormone (GHRH)-stimulated GH release was evaluated in six GH-deficient children during long term therapy with GHRH. Nocturnal GH concentrations were determined every 20 min for 12 h under the following four conditions: 1) control, 2) atenolol administration only, 3) sc GHRH administration only, and 4) combined GHRH and atenolol administration. The mean 12-h nocturnal GH concentrations after administration of atenolol alone [2.4 +/- 0.6 microgram/L (mean +/- SEM)] or GHRH alone (2.7 +/- 1.0 micrograms/L) were indistinguishable from baseline values (2.0 +/- 0.5 microgram/L; P greater than 0.05). In contrast, the addition of atenolol to ongoing GHRH therapy caused a clear augmentation of 12-h overnight GH release compared to that during all other study periods (5.0 +/- 1.3 micrograms/L; P less than 0.05). In a subset of three subjects for whom GH pulse characteristics were determined, the primary mode of the enhanced GH release was through an increase in the amplitude of serum GH pulses. These results are consistent with the hypothesis that beta-adrenergic blocking compounds enhance the responsivity of the pituitary gland to agents that permit GH release by inhibiting hypothalamic somatostatin secretion or action. They suggest that atenolol may have potential as an adjunctive therapy in some children with abnormalities of GH secretion when GHRH is the primary therapeutic agent.
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PMID:Atenolol enhances nocturnal growth hormone (GH) release in GH-deficient children during long term GH-releasing hormone therapy. 210 29

We investigated the role of neuropeptides and adrenergic agonists in the regulation of intracellular 3',5'-cyclic adenosine monophosphate (cyclic AMP) contents in cultured Schwann cells from sciatic nerve of neonatal Sprague-Dawley rats. Of the neuropeptides examined, vasoactive intestinal polypeptide (VIP) and secretin markedly stimulated the accumulation of intracellular cyclic AMP in a time- and dose-dependent manner with half maximum at 3 and 12 min, and 2.8 X 10(-5) and 5.0 X 10(-5) M, respectively. While somatostatin, substance P, adrenocorticotropin (ACTH), beta-endorphin, and nerve growth factor (NGF) did not show any effect on cyclic AMP metabolism, isoproterenol (IP), norepinephrine (NE) and epinephrine (E) also markedly elevated the Schwann cell cyclic AMP concentration. The rank-order of potency of these adrenergic catecholamines on cyclic AMP accumulation was isoproterenol greater than norepinephrine greater than epinephrine. Simultaneous addition of VIP or secretin to the Schwann cell culture synergistically enhanced the norepinephrine-induced elevation of intracellular cyclic AMP. The effect of norepinephrine was antagonized by a selective beta 1-adrenergic antagonist but not by beta 2- nor alpha-adrenergic antagonists. These results suggest that VIP, secretin, and beta 1-adrenergic agonists alone or synergistically may play a part in the regulation of metabolism of Schwann cells mediated through a cyclic AMP-dependent mechanism.
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PMID:Peptidergic and adrenergic regulation of the intracellular 3',5'-cyclic adenosine monophosphate content in cultured rat Schwann cells. 285 16

Drugs used to treat portal hypertension cause constriction of mesenteric arterioles, reducing inflow to the portal venous system, portal pressure, and flow through portasystemic collaterals (such as esophageal varices). Vasopressin and somatostatin are direct vasoconstrictors. Propranolol acts by blocking vasodilatory beta 1 receptors and reducing cardiac output. A major side effect of vasopressin therapy is impaired cardiac performance secondary to coronary vasoconstriction and increased work against high arterial pressure. Infusion of vasopressin together with a cardiac inotrope or a vasodilator, and administration of vasopressin as an inactive "hormonogen" which is slowly released in vivo, may lessen adverse effects. Somatostatin appears to act selectively in the mesenteric circulation. Controlled trials indicate that vasopressin may be useful for controlling hemorrhage from esophageal varices and that somatostatin works at least as well as vasopressin. Propranolol treatment has been used to prevent variceal bleeding; however, controlled trials of its effectiveness have produced conflicting results.
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PMID:Drug therapy for portal hypertension. 287 47

The purpose of the present study was to evaluate whether the inhibitory effects of beta-adrenergic agonists on gastric secretory activity in vivo could be mediated through a local release of somatostatin. The gastric secretion was measured during continuous stimulation with pentagastrin (1 microgram/kg/h). The infusion of isoprenaline (beta 1 + beta 2), salmefamol (beta 2), and somatostatin produced inhibitory effects on both acid and pepsin secretion. The reaction patterns were similar for isoprenaline and somatostatin, whereas salmefamol induced an inhibition of longer duration and with dissimilar dose-response kinetics. The gastric somatostatin release was significantly increased after infusion of both beta-adrenergic agonists and somatostatin, with patterns similar to those obtained for the secretory inhibition. There was a significant correlation between the somatostatin release and the acid and pepsin secretion during infusion of the secretory inhibitors but not in the control state. This study shows that beta-adrenergic agonists have inhibitory effects on gastric secretion in vivo similar to those of somatostatin. Both somatostatin and the beta-adrenergic agonists stimulated the release of somatostatin from the gastric mucosa. beta-Adrenergic antagonists were without effects. Somatostatin thereby fulfils the requirements for an endogenous mediator of the beta-adrenergic inhibition.
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PMID:Beta-adrenergic agonists inhibit gastric acid and pepsin secretion through somatostatin release in dogs. 287 15

The growth hormone (GH) responses to a single bolus injection of the growth hormone releasing hormone (GRH) were examined in the basal state and in the presence of beta-adrenergic receptor blocking agents of different specificity in ten normal men. During a constant five-hour infusion of 56 micrograms/min of propranolol (nonselective beta-adrenergic receptor-blocker) in seven subjects studied, there was a significant augmentation of the GH release in response to exogenous GRH compared to the GH response during saline infusion, as measured by the peak serum GH concentrations after GRH (P = 0.019) and the integrated GH values (P = 0.019). A similar significant enhancement of GH responses to exogenous GRH as compared to the control day was observed with the specific beta 1-adrenergic receptor-blocker atenolol in all seven subjects studied (four of whom also participated in the propranolol study). Both the peak GH response to a GRH bolus and the integrated GH values were significantly greater with atenolol (P = 0.019 for both). There was no difference in serum GH concentrations after beta-adrenergic receptor-blocking drugs during a three-hour sampling period before GRH administration compared to placebo. Our results support the concept that beta-adrenergic receptors may modulate either the release or action of hypothalamic somatostatin in the control of GH secretion in man. We suggest the effect is mediated by specific beta 1-adrenergic receptors.
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PMID:Selective beta 1-adrenergic receptor-blockade with atenolol enhances growth hormone releasing hormone and mediated growth hormone release in man. 288 5

Muscle strips from the fundus, trigone, and distal ureter obtained from children at operation for vesicoureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and the transmitter causing contraction of the detrusor muscle was regarded as being acetylcholine. The adrenergic innervation was very sparse except around the ureteric orifices. No contractile alpha-adrenoceptors could be detected but beta-receptor-mediated relaxation was found. The type was not beta 1 or beta 2, suggesting a third type of beta-receptor. Peptidergic nerves containing vasoactive intestinal peptide (VIP) were demonstrated in a few nerve terminals. No nerves containing enkephalin, somatostatin, or substance P were found. VIP affected the detrusor muscle, indicating a possible role as a modulator of transmitter action. Imipramine, used for enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, making it suitable for treatment of diurnal enuresis.
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PMID:Urinary bladder innervation in children. 355 68

The effect of adrenergic agonists and antagonists on the secretion of gastric somatostatin-like immunoreactivity (SLI) and gastrin was investigated in an isolated, vascularly perfused rat stomach preparation. Two- to six-fold increases in SLI secretion induced by isoproterenol, epinephrine, and norepinephrine were completely abolished by propranolol but were not influenced by phentolamine. Propranolol did not alter glucagon- and DB-cAMP-induced stimulation of SLI release. Experiments in which the beta 2-agonist salbutamol and the beta 1- and beta 2-blockers practolol and H35/25 were used showed that both subtypes of beta receptors are involved. Gastrin secretion revealed only minor changes in dose-response studies with a wide range of isoproterenol concentrations (2 X 10(-8) to 1.5 X 10(-4) M). The results obtained in this study suggest that in rats 1) the SLI response to adrenergic agonism is predominantly mediated by beta receptors; 2) both beta 1- and beta 2-adrenergic receptors are involved; 3) under in vitro conditions, adrenergic agonism is a weak stimulus for gastrin secretion.
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PMID:Adrenergic control of rat gastric somatostatin and gastrin release. 614 72


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