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)

The effects of rat growth hormone releasing factor (rGRF) on somatostatin (SRIF) secretion, cyclic nucleotide production and phosphatidylinositol metabolism were investigated in the median eminence (ME), using an in vitro system. Medium was discarded and replaced by medium containing various concentrations of rGRF or rGRF plus epinephrine (E, 6 x 10(-7) M). rGRF had no effect on basal or E-stimulated release of cAMP. In the same experiments rGRF markedly stimulated SRIF release. These results suggested that cAMP is not involved in the stimulatory effect of GRF on SRIF release. However, GRF significantly stimulated release of both SRIF and cGMP in a dose-related manner. Maximal stimulation was observed at 10(-10) M GRF (p less than 0.005) which also produces maximal SRIF release. 2'0-monobutyrylguanosine 3'5' cyclic phosphate (mbcGMP, 10(-11) to 10(-10) M) stimulated SRIF release from ME fragments (p less than 0.001 at 10(-10) M) whereas the control, sodium butyrate (10(-6) M), had no effect. GRF caused significant elevation of 30.6% in the concentration of labelled inositol phosphates [( 3H]-IPs) in the ME. These data indicate that GRF stimulation of SRIF release is accompanied by increased cGMP production and phosphatidyl-inositol (PI) metabolism but does not alter cAMP production. Because mbcGMP can directly stimulate SRIF release, we suggest that GRF causes a receptor-mediated increase in the metabolism of phosphatidylinositol and cGMP formation. These actions therefore may be among the early metabolic events in the mechanism of GRF-stimulated SRIF release from the ME.
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PMID:Rat growth hormone-releasing factor stimulates cyclic GMP formation and phosphatidylinositol metabolism in the median eminence. 167 56

In light of the effects of gastrointestinal (GI) peptides on bile secretion and biliary tract mobility, we studied the effects of GI peptides on gallstone formation in guinea pigs fed on low protein lithogenic diet. The peptides under study included cholecystokinin octapeptide (CCK-8), vasoactive intestinal peptide (VIP), somatostatin (SRIF), secretin (SEC), and neurotensin (NT). Hepatic bile flow, electrolytes, and other bile components were also measured. It was found that CCK-8 and VIP suppressed the formation of gallstones and increased hepatic bile flow and Na+, K+, Cl- output significantly. On the other hand, SRIF significantly promoted gallstone formation. The rates of gallstone formation in CCK-8, VIP, and SRIF treated guinea pigs were 15.4%, 23.5%, and 88.0%, respectively, in contrast to 56.8% in the control group. The inhibitory effect of CCK-8 and promoting effect of SRIF on gallstone formation were dose-dependent.
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PMID:Effects of gastrointestinal peptides on formation of gallstone in guinea pigs. 167 24

The direct action of somatostatin on smooth muscle was examined in muscle cells isolated from the stomach and intestine of human and guinea pig. Somatostatin inhibited relaxation in gastric but not intestinal muscle cells of the two species, and its mechanism of action was explored in more detail in gastric muscle cells of the guinea pig. Somatostatin inhibited relaxation induced by vasoactive intestinal peptide (VIP, 83 +/- 7%, P less than 0.001) and isoproterenol (85 +/- 5%, P less than 0.001), as well as the concomitant increase in adenosine 3',5'-cyclic monophosphate (cAMP) production [81 +/- 25% inhibition with VIP (P less than 0.02) and 68 +/- 12% inhibition with isoproterenol (P less than 0.01)]. Inhibition of relaxation and cAMP production was abolished by pretreatment of the cells with pertussis toxin. Relaxation induced by the permeant derivative of cAMP, N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate, by sodium nitroprusside, which acts by increasing levels of guanosine 3',5'-cyclic monophosphate, or by ATP, which acts by opening of K+ channels, was not affected by somatostatin. The fact that inhibition by somatostatin and its reversal by pertussis toxin was confined to agonists that stimulate an increase in the levels of cAMP implied that somatostatin acts by inhibiting the generation and not the action of cAMP. It is concluded that somatostatin receptors on gastric muscle cells mediate inhibition via a GTP-binding, pertussis-sensitive regulatory protein, Gi, coupled to adenylate cyclase.
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PMID:Inhibition of muscle cell relaxation by somatostatin: tissue-specific, cAMP-dependent, pertussis toxin-sensitive. 167 35

Rat cerebral cortex synaptosomes were exposed in superfusion to various depolarizing stimuli and the release of somatostatin-like immunoreactivity (SRIF-LI) was measured by means of a radioimmunoassay procedure. High KCl (9-50 mM) concentration dependently evoked SRIF-LI release; the evoked overflow reached a plateau at 25 mM KCl and was completely abolished when Ca2+ ions were omitted from the superfusion medium, independently of the concentration of KCl used. The 15 mM K(+)-evoked release of SRIF-LI increased sharply as the Ca2+ concentration was raised to 0.8 mM, then leveled off and reached a plateau at 1.2 mM. The 15 mM K(+)-evoked overflow, but not the spontaneous outflow, was partially decreased (50%) by 1 microM tetrodotoxin. The presence in the superfusion fluid of a mixture of peptidase inhibitors did not improve the recovery of SRIF-LI both in the absence and in the presence of high K+. Exposure of synaptosomes to veratrine (1-50 microM) induced release of SRIF-LI in a concentration-dependent way. The effect of the alkaloid was strictly Ca2+ and tetrodotoxin sensitive. Replacement of extracellular Na+ by sucrose caused an acceleration of the spontaneous SRIF-LI outflow that was inversely correlated to the Na+ content in the superfusion medium. The release evoked by the sodium-deprived media did not exhibit any calcium dependence. HPLC analysis of the samples collected during superfusion showed that greater than 90% of the SRIF-LI released either during the spontaneous outflow or by 15 mM KCl was represented by SRIF-14 (SRIF-28(14-28]. These values reflected the ratio SRIF-14/SRIF-28 found in synaptosomes at the end of the experiments.
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PMID:Somatostatin release from rat cerebral cortex synaptosomes. 168 Jan 60

The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0 +/- 0.25 vs 2.4 +/- 0.2 ng AngI/ml/h; p less than 0.01) and glucagon levels (40 +/- 11 vs 20 +/- 16 pg/ml; p less than 0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE2, and PGF2 alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r = 0.7; p less than 0.001) and urinary prostaglandin E2 and glomerular filtration (r = 0.52; p less than 0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.
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PMID:Effect of somatostatin on kidney function and vasoactive hormone systems in health subjects. 168 Nov 32

The renal effect of cyclic somatostatin was studied on healthy subjects. The somatostatin was used at therapeutical dose in intravenous infusion. Somatostatin decreases the renal plasma flow, glomerular filtration rate, osmotic and free water clearances, sodium and potassium excretion and the tubular reabsorption of phosphorus while urinary osmolality increases. Under somatostatin infusion the urinary excretion of catecholamines, PGE2, PGF2 alfa and the plasma renin activity and the plasma concentration of glucagon and growth hormone decrease. The antidiuretic activity of somatostatin is due to a) a direct haemodinamic effect, b) an influence on the renal tubular transport as well and also c) because of change the water handling in the collecting ducts.
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PMID:[Effect of somatostatin on kidney function]. 168 89

To elucidate the mechanism by which carbamazepine lowers somatostatin concentration in cerebrospinal fluid of humans, the effect of carbamazepine on secretion of this peptide was studied in rat cerebral cell cultures. Concentrations of carbamazepine within the therapeutic range (4 x 10(-5) M) inhibited spontaneous release of somatostatin and blocked secretory responses to the epileptogen, picrotoxin, and to the cyclic cAMP stimulator forskolin. One of the proposed mechanisms of carbamazepine action is that it binds to adenosine receptors, but in this study, aminophylline, an adenosine antagonist, in a concentration as high as 2.4 x 10(-4) M, did not reverse carbamazepine effects. Carbamazepine suppression of picrotoxin, however, was overcome by exposure to veratridine, a sodium channel-active compound. This finding supports the hypothesis that carbamazepine acts by binding to sodium channels. Phenytoin, another anticonvulsant with many similar properties, also blocked picrotoxin-induced somatostatin release at a concentration of 10(-4) M, and its effects were also reversed by veratridine at a concentration of 10(-5) M. These findings clarify the mechanism by which carbamazepine and phenytoin act in epilepsy and trigeminal neuralgia.
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PMID:Carbamazepine and phenytoin inhibit somatostatin release from dispersed cerebral cells in culture. 168 80

The effects of somatostatin (SS) on the treatment of acute pancreatitis were studied in rats. Acute pancreatitis was established by injecting 5% sodium taurocholate in the biliopancreatic duct. Previously, pancreatic necrosis was determined in this experimental model at several intervals without treatment. Treatment was started according different groups: at 12, 16 and 20 hours after induction of acute pancreatitis (IV bolus of 4 ug/kg body weight followed by a 24h continuous infusion of 4 ug/kg body wt/hour). When somatostatin was initiated at 12 or 16h a decrease in serum amylase and lactodehydrogenase was observed, as well as in pancreatic necrosis resulting in 0% mortality after 24h of treatment. When somatostatin was started at 20h there was no changes in the lethal outcome of the disease.
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PMID:[Somatostatin in the treatment of established and severe acute pancreatitis in the rat]. 168 78

1. Somatotrophs from enzymatically dispersed anterior pituitary glands of rats, enriched to greater than 94% purity by density gradient centrifugation, were studied within 16 h of isolation using patch clamp recording methods in the conventional whole-cell and the perforated-patch configurations. 2. Rhythmic oscillations of membrane potential gave rise to action potentials in thirty-six of fifty-two cells studied with the perforated-patch technique. Membrane potential oscillated between approximately -70 mV and approximately -25 mV with an average frequency (mean +/- S.D.) of 0.9 +/- 0.9 s-1. 3. The current-voltage (I-V) relationship of cells was linear at negative potentials with outward rectification at potentials positive to -40 mV. Evidence that the outward current was due to K+ channels came from the deactivation tail currents, which reversed direction close to the K+ equilibrium potential (EK). The reversal potential shifted 60 mV per tenfold change of external K+ concentration ([K+]o), as expected for K+ current. 4. Suppression of outward current by tetraethylammonium (TEA) provided additional evidence for K+ current. Cd2+ reduced outward current, suggesting the presence of Ca(2+)-activated K+ conductance. 5. Depolarizing commands elicited transient inward Na+ current and a sustained Ca2+ current (ICa). ICa was recorded in isolation with Cs+ and TEA in the recording pipette and 10 mM-Ba2+ as the charge carrier. Activation of ICa began at approximately -40 mV, with peak inward current at 0 to +10 mV. The half-inactivation potential was approximately -35 mV. In addition, ICa was blocked by nifedipine. These characteristics indicate the presence of L-type Ca2+ channels in somatotrophs. 6. Somatostatin caused hyperpolarization and suppressed the spontaneous bursts of action potentials. Under voltage clamp, somatostatin activated an inwardly rectifying current that reversed direction near EK. When EK was altered by elevation of [K+]o, the reversal potential of the somatostatin-induced current shifted 55 mV per tenfold change of [K+]o, as predicted for a K+ current by the Nernst relation. The somatostatin-induced conductance (gK) was greater at more negative potentials, and the activation range shifted positive with elevation of [K+]o. 7. We conclude that freshly isolated rat somatotrophs possess Na+, Ca2+ and K+ currents. A large proportion of the cells exhibit spontaneous bursts of action potentials. Somatostatin activates an inwardly rectifying K+ conductance, causing hyperpolarization and cessation of spontaneous action potential activity, actions that would contribute to suppression of growth hormone release.
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PMID:Somatostatin activates an inwardly rectifying K+ conductance in freshly dispersed rat somatotrophs. 168 49

The uptake of the cyclopeptide c(Phe-Thr-Lys-Trp-Phe-D-Pro) (008), an analog of somatostatin with retro sequence, was studied in isolated hepatocytes. 008 is taken up by hepatocytes in a concentration-, time-, energy- and temperature- dependent manner. Since 008 is hydrophobic, it binds rapidly to liver cells. This is evident by the positive intercept at the gamma-axis in the uptake curves. At higher concentrations, a minor part of the transport occurs by diffusion at a rate of 8.307.10(-6) cm/s. This part of diffusion is measured at 4 degrees C and can be subtracted from the uptake at 37 degrees C resulting in the carrier mediated part of uptake which is saturable. Kinetic parameters for the saturable part of uptake are Km 1.5 microM and Vmax 40.0 pmol/mg per min. The transport is decreased in the absence of oxygen and in the presence of metabolic inhibitors. Uptake is accelerated at temperatures above 20 degrees C. The activation energy was determined to be 30.77 kJ/mol. The membrane potential and not a sodium gradient is the main driving force for 008 transport. Cholate (a typical substrate of the multispecific bile acid transporter) and taurocholate are mutual competitive inhibitors of 008 uptake. Phalloidin, antamanide and iodipamide, typical foreign substrates of the transporter, interfere with the uptake of 008. AS 30D ascites hepatoma cells, known to be unable to transport bile acids, phalloidin and iodipamide, are also unfit to transport 008. Interestingly, sulfobromophthalein (BSP) but not rifampicin, both foreign substrates of the bilirubin carrier, inhibits the transport of 008 in a competitive manner.
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PMID:Hepatocellular transport of cyclosomatostatins: evidence for a carrier system related to the multispecific bile acid transporter. 170 41


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