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)

In the present study the possible influence of capsaicin on human arterial coronary tone in vitro was studied in relation to the vasodilatory properties of calcitonin gene-related peptide (CGRP), substance P (SP) or neurokinin A (NKA). In addition, the influence of vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) on the arteries was investigated. CGRP application to potassium-pre-contracted human epicardial coronary arteries (0.4-0.6 mm in inner diameter) induced a concentration-dependent, long-lasting relaxation. SP also relaxed these pre-contracted arteries, but the relaxation was transient and tachyphylaxis developed rapidly upon repeated administration. SP tachyphylaxis did not influence the relaxatory effects of CGRP. Furthermore, pre-incubation with gossypol, an inhibitor of the formation and release of endothelium-derived relaxing factors (EDRF), completely abolished the effects of SP without influencing the dilatory action of CGRP. NKA only induced a very minor relaxation of the pre-contracted arteries. Both VIP and SOM concentration-dependently relaxed the pre-contracted arteries. Capsaicin evoked a relaxation of the potassium-pre-contracted arteries. This effect was not influenced by SP tachyphylaxis or gossypol incubation. Thus, CGRP but not SP mimics the vasodilatory effects of capsaicin on human coronary arteries. This suggests that CGRP rather than SP is likely to mediate the relaxatory effects seen upon activation of cardiac sensory nerves.
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PMID:Capsaicin-induced vasodilatation of human coronary arteries in vitro is mediated by calcitonin gene-related peptide rather than substance P or neurokinin A. 247 11

Six patients with short intestine (jejunal length 25-70 cm) on long-term parenteral nutrition, needing 4-5 L of intravenous fluid daily, were given octreotide (a somatostatin analogue, SMS 201-995) to investigate whether it would reduce beneficially their secretory diarrhoea (3.6-6.9 kg/day). They consumed the same diet for 2 control days, followed by 2 test days. Octreotide was given intravenously, initially in a dose of 50 micrograms b.d. through the central feeding line. There was a significant reduction of daily stomal output (0.5-5.0 kg) and daily sodium and potassium output; however there was no significant change in energy absorption. The response to octreotide was greatest in those patients who absorbed least nutrients. A dose increase to 100 micrograms t.d.s. gave no further measurable benefit though the patients found it smoothed-out the post-prandial rise in stomal output. Two patients were continued on long-term octreotide therapy, which allowed for a daily reduction in intravenous fluid of 1 and 1.5 L. Octreotide's anti-secretory effect was found to have been maintained when it was retested in one patient after a year of continuous therapy.
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PMID:Octreotide (a somatostatin analogue) improves the quality of life in some patients with a short intestine. 251 50

VIP-secreting tumors are rare, but they produce a dramatic clinical picture, the most prominent feature of which is profuse, watery diarrhea and hypokalemia. A definitive diagnosis is aided by the determination of plasma VIP concentrations through the use of the sensitive radioimmunoassays that are now available. Intestinal secretion resulting from the direct action of VIP on the intestinal epithelial cell receptors accounts for the loss of fluid and electrolytes in patients with VIPoma. The hypokalemia is the result of passive and VIP-induced active secretion of potassium by colonic epithelial cells. Surgery is the most definitive treatment of VIPoma; pharmacotherapy is extremely important in controlling symptoms and stabilizing the patient prior to surgery. Sandostatin and glucocorticoids are well established agents in the management of the secretory diarrhea; other pharmacologic agents, including clonidine, indomethacin, phenothiazines, lithium carbonate, and propranolol, may be helpful in selected patients but require further study. The most potent and promising drug for the treatment of VIPoma is a new peptidomimetic agent--Sandostatin. This metabolically stable synthetic analogue of somatostatin appears, in part, to inhibit the release of VIP from the tumor and the secretion of chloride by the intestine. In addition to controlling the diarrhea, it may have a direct effect on the tumor in reducing its size.
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PMID:Medical therapy of VIPomas. 254 44

Somatostatin is a peptide that has anticholeretic properties in the dog. The purpose of the present work was to investigate if somatostatin is an anticholeretic agent in humans also. The effects of intravenous infusion of somatostatin on hepatic bile flow and biliary electrolytes and secretion of biliary lipids were studied in 7 patients with complete biliary drainage who had been operated on for choledocholithiasis. Somatostatin, 250 microgram/h, was found to decrease the hepatic bile secretion by approximately 30%. The peptide also reduced the outputs of bile acids, cholesterol, and phospholipids and the outputs of sodium, potassium, and chloride. The concentrations of the biliary lipids were not significantly changed. Somatostatin inhibited the erythritol clearance in the 2 patients studied by approximately 25%. The present study thus provides evidence that somatostatin inhibits bile formation in humans. It appears as if the reduction in bile production is mainly due to decreased canalicular bile flow. It is possible that this effect of somatostatin is attributable to inhibition of bile acid synthesis or of transport-secretion of bile acids, or both.
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PMID:Effects of somatostatin on hepatic bile formation. 256 34

Terbutaline, a beta 2-adrenergic agonist, has been shown to cause hypokalemia and an increase of plasma glucose and serum insulin concentrations. We considered that terbutaline-induced hypokalemia may be due to the insulin-induced shift of potassium (K+) from the extracellular to the intracellular space. If so, then inhibition of insulin secretion by somatostatin would prevent terbutaline-induced hypokalemia. Further, we wondered whether oral potassium pretreatment could prevent terbutaline-induced hypokalemia. Therefore, 10 healthy volunteers (5 men, 5 women; mean age, 23 yr +/- 3 SD) received either sodium chloride (NaCl) or somatostatin intravenously together with 0.25 mg terbutaline subcutaneously in a double-blind crossover design. On a third test day, they received 39 mval of K+ powder orally before terbutaline injection in an open trial. Terbutaline caused a significant decrease of K+ (from 3.96 +/- 0.08 to 3.3 +/- 0.13 mmol/L +/- SEM; p less than 0.0005), accompanied by a significant increase in plasma glucose (from 83 +/- 3.6 to 101 +/- 4.4 mg/dl +/- SEM; p less than 0.01) and serum insulin concentrations (from 11.7 +/- 0.9 to 19.9 +/- 1.1 microU/ml +/- SEM; p less than 0.001), confirming earlier data. Somatostatin pretreatment inhibited the terbutaline-induced hypokalemia; the small fall of K+ (from 3.7 +/- 0.08 to 3.5 +/- 0.2 mmol/L) was no longer significant. Insulin secretion was completely blocked by somatostatin, leading to an even more pronounced increase of blood glucose. Hypokalemia after terbutaline injection was not prevented by oral potassium pretreatment. In summary, the present findings confirm that terbutaline-induced hypokalemia is associated with increased plasma glucose and insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of somatostatin and oral potassium administration on terbutaline-induced hypokalemia. 256 17

Rat hypothalamic somatostatin (SRIF) release in vitro is inversely related to medium glucose concentration and is stimulated by agents interfering with neural glucose uptake or metabolism. The present studies examined monosaccharide specificity of this effect by comparing the ability of glucose and nonmetabolized sugars (ribose, fructose, and galactose) to reverse glucopenia-mediated SRIF release. Removal of glucose from incubation medium resulted in a 7-fold stimulation of hypothalamic SRIF release (24.9 +/- 3.0 to 169.0 +/- 46.2 pg/5 min) that was promptly and fully reversed by readdition of glucose (21.5 +/- 6.0 pg/5 min). Depolarizing concentrations of potassium (40 mM) added to medium after incubation in the presence or absence of glucose produced similar 4-fold biphasic stimulation of SRIF release, suggesting that tissue viability was unimpaired by short term glucopenia. By contrast, nonmetabolized sugars (ribose, fructose, or galactose) at concentrations up to 28 mM were unable to reverse glucopenia-mediated hypothalamic SRIF release. These findings suggest that neural metabolism of glucose specifically influences hypothalamic SRIF release, an effect likely to depend on glycolysis with resulting energy production. This explanation is supported by the finding that the glycolytic intermediates dihydroxyacetone and glyceraldehyde were partly, and pyruvate completely, able to restore glucopenia-mediated SRIF release toward basal, with a maximal effect at 14 mM. Our present studies suggest that rat hypothalamic SRIF release reflects ambient glucose status, is stimulated by glucopenia, and may explain inhibition of GH secretion in the rat during hypoglycemia.
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PMID:Glucopenia-mediated release of somatostatin from incubated rat hypothalamus: monosaccharide specificity and role of glycolytic intermediates. 256 42

Regulation of preprosomatostatin mRNA and tyrosine hydroxylase mRNA were examined in sympathetic neurons of the rat superior cervical ganglion (SCG). Surgical denervation of the adult SCG increased ganglion levels of preprosomatostatin (SS) mRNA more than 11-fold, and levels of the mRNA remained elevated 14 days after surgery. By contrast, denervation decreased levels of tyrosine hydroxylase (TH) mRNA. Potassium- or veratridine-induced membrane depolarization of cultured neonatal sympathetic neurons decreased levels of SS mRNA but elevated levels of TH mRNA. Sodium channel blockade with tetrodotoxin prevented the effects of veratridine on SS and TH mRNAs. In toto these observations suggest that transsynaptic nerve impulse activity and sympathetic neuron membrane depolarization decrease SS synthesis but increase TH synthesis at the mRNA level. Thus nerve impulse activity may alter the relative levels of different transmitters co-expressed in the same neuronal population by inhibiting levels of some species of mRNA while simultaneously stimulating levels of others.
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PMID:Differences in the effects of membrane depolarization on levels of preprosomatostatin mRNA and tyrosine hydroxylase mRNA in rat sympathetic neurons in vivo and in culture. 256 23

Currents through single-ion channels were recorded in the cell-attached configuration from locus ceruleus neurons enzymatically dissociated from newborn rats. When the selective mu opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol was in the patch-clamp electrode, unitary inward currents were observed with conductance of approximately 45 pS (measured at zero pipette potential, with 150 mM potassium in the recording electrode). Long silences, lasting many seconds to minutes, separated periods of activity of similar durations. Within such activity periods the distribution of closed times of the channels was best fitted by the sum of two exponential functions (time constants approximately 1 and 30 ms), and the durations of channel openings were fit by a single exponential function; mean open time increased from 2 to 120 ms as agonist concentration increased. Channel activity was not seen when high concentrations of opioids were applied to the neuron outside the patch-clamp recording electrode, indicating intimate coupling between receptor and potassium channel. Unitary currents with similar properties were also seen when pipettes contained alpha 2 adrenoceptor agonists or somatostatin. Taken with previous findings, the results indicate that mu opioid receptors, alpha 2 adrenoceptors, and somatostatin receptors can couple directly to membrane potassium channels through the local intermediary action of a GTP binding protein.
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PMID:Single potassium channels opened by opioids in rat locus ceruleus neurons. 256 72

The concept of multifactorial pituitary control is now well established. As in other cell systems, integration of complex messages involves dynamic interactions of receptors and coupling mechanisms. Regulation of adenohypophyseal secretions has been shown to involve cyclic AMP production, the modulation of phosphatidylinositol phosphate breakdown and Ca2+ mobilization. Dopamine, somatostatin and angiotensin II receptors are negatively coupled to adenylate cyclase in anterior pituitary cells. In the case of angiotensin, this effect on adenylate cyclase appears paradoxical since the peptide markedly stimulates prolactin secretion. In fact, angiotensin II also markedly stimulates inositol phosphate production and this effect could account for the stimulated hormone secretion. In addition, dopamine could inhibit inositol phosphate production stimulated by angiotensin II and thyrotropin-releasing hormone. Dopamine and somatostatin also directly modulate voltage-dependent calcium channels, perhaps through a direct coupling with potassium channels. On the other hand, steroids modulate the sensitivity of adenohypophyseal cells to neurohormones by different mechanisms. In the case of somatostatin, it increases the number of specific binding sites, while in the case of dopamine estradiol affects the transduction mechanisms of D2 dopamine receptors. In conclusion, dopamine and somatostatin receptors appear coupled to various transduction mechanisms through pertussis-sensitive G proteins in anterior pituitary cells.
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PMID:Multiple transduction mechanisms of dopamine, somatostatin and angiotensin II receptors in anterior pituitary cells. 256 74

omega-Conotoxin GVIA (omega-CT) diminished the potassium-induced in vitro release of 3H-gamma-aminobutyric acid (3H-GABA) from slices of rat neostriatum in a manner which depended on the concentration of potassium. omega-CT (0.1 mmol/l) decreased the release of 3H-GABA induced by 25 mmol/l K+ from 11.6% to 6.1% of tissue content, ie. by 48%, while it did not affect the release of 3H-GABA caused by 20 mmol/l K+, which was 4.8% of tissue content. However, in the presence of a polyclonal antiserum or cysteamine (600 mumol/l), both of which diminish the effects of endogenous somatostatin, 0.1-10 nmol/l omega-CT decreased the release of 3H-GABA induced by 20 mmoles/l K+ by 40%. It is concluded that omega-CT did not only inhibit GABA-neurones, but had an additional inhibitory effect on somatostatin neurones which are known to depress the release of 3H-GABA. It is further concluded that neuronal interactions, which are possible in brain slice preparations, may impede the interpretation of effects of drugs, especially if agents are used which affect basic mechanisms of transmitter release and thus the release of various transmitters from neurones.
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PMID:Effect of omega-conotoxin GVIA on release of 3H-gamma-aminobutyric acid from slices of rat neostriatum. 256 33


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