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 is a hypothalamic tetradecapeptide with many central nervous system actions. We investigated a potential role for altered somatostatin activity in affective disorder by measuring somatostatin in the cerebrospinal fluid (CSF) of 47 patients with affective disorder and of 39 normal volunteers. Medication-free depressed patients showed significantly lower levels of CSF somatostatin than normal volunteers (p less than .001) or patients during the improved state (p less than .01). Somatostatin levels were significantly and inversely correlated with duration of sleep on the night of the lumbar puncture (p less than .05). Treatment with carbamazepine reduced CSF somatostatin (p less than .01) in contrast to the absence of effect of imipramine, desmethylimipramine, and lithium carbonate and the significant increase in CSF somatostatin seen in a small group of patients treated with zimelidine. The implications of these findings with respect to attempts to explore the neurobiology of depression are discussed.
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PMID:CSF somatostatin in affective illness and normal volunteers. 286 61

While it is well known that large doses of somatostatin inhibit human pancreatic enzyme secretion, it is still unknown whether low doses are also effective and whether the peptide is able to inhibit bicarbonate production. Eight subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery were studied. Somatostatin was infused at progressively increasing rates of 0.05, 0.15, 0.45, and 1.35 micrograms/kg/hr, for 30 min/dose, during pancreatic stimulation with secretin, 25 ng/kg/hr, and cerulein, 10 ng/kg/hr. Somatostatin, at the dose of 0.05 microgram/kg/hr (shown to produce blood levels similar to those measured after a meal) did not affect pancreatic secretion in any of the subjects. The successive three higher doses caused a significant and dose-dependent inhibition of protein concentration and output and of bicarbonate output. Bicarbonate concentration was slightly but significantly reduced only by the two highest doses of somatostatin. At each dose level, the inhibition of protein output was much more marked than the inhibition of bicarbonate output. The maximal inhibition of protein output (at 1.35 micrograms/kg/hr somatostatin) was 73.9 +/- 5.4%, and that of bicarbonate output was 55.9 +/- 6.4%. The results demonstrate that: (1) the administration of somatostatin at a low dose level does not affect human exocrine pancreatic secretion, at least under the experimental conditions of this study; and (2) the administration of larger doses of somatostatin inhibits pancreatic secretion of both protein and bicarbonate dose-dependently. The inhibitory effect on protein output is significantly greater than that on water and bicarbonate production.
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PMID:Effect of somatostatin 14 on pure human pancreatic secretion. 288 7

The role of gut hormones, such as secretin and CCK, in the stimulation of pancreatic secretion by duodenal HCl or oleate and by meat feeding has been studied in conscious dogs before and after pretreatment with atropine and somatostatin. Plasma hormones were measured by specific and sensitive radioimmunoassays. Duodenal perfusion with HCl and oleate stimulated dose-dependently pancreatic HCO3 and protein secretion and raised plasma levels of secretin and CCK, respectively. Atropine reduced significantly both HCO3 and protein secretion but did not affect plasma secretin and CCK levels in these studies. Both exocrine pancreatic secretion and plasma secretin and CCK levels were suppressed by somatostatin. Meat feeding caused a marked pancreatic HCO3 and protein secretion accompanied by a significant increase in plasma secretin and CCK which seem to play an important role in the postprandial pancreatic stimulation. Both atropine and somatostatin reduced the pancreatic secretion induced by exogenous hormones but only somatostatin, but not atropine, significantly decreased plasma secretin and CCK responses to intestinal stimulants. We conclude that both atropine and somatostatin reduce the pancreatic responses to duodenal HCl or oleate or to meat feeding but only somatostatin is capable of suppressing the release of secretin and CCK.
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PMID:Role of secretin and CCK in the stimulation of pancreatic secretion in conscious dogs. Effects of atropine and somatostatin. 289 Jun 95

1. Studies of gastric function were made in preruminant calves fitted with a single abomasal cannula, re-entrant cannulas in the duodenum close to the pylorus and recording electrodes on the pyloric antrum and proximal duodenum. 2. Simultaneous measurements were made of gastric emptying of a saline (9 g sodium chloride/l) meal, myoelectric activity of antral muscle and plasma concentration of somatostatin in jugular blood whilst infusing the duodenum with different solutions. The duodenal infusates were isotonic sodium bicarbonate (300 mosmol/kg), hyperosmolar solutions of NaCl (1000 mosmol/kg), sodium carbonate (500 mosmol/kg), sucrose (1000 mosmol/kg), 41 g emulsified butterfat/kg or 60 mM-hydrochloric acid. 3. Infusing the duodenum with isotonic NaHCO3 stimulated intense myoelectric activity of the antral smooth muscle and rapid emptying of the test meal. In contrast, infusions of 60 mM-HCl reduced antral motility and inhibited gastric emptying of digesta. This inhibitory response to HCl infusion was related to a significant (P less than 0.05) increase of somatostatin in peripheral venous blood. 4. The Na2CO3 infusate, like HCl, inhibited gastric motor activity and digesta emptying, but the concentration of circulating somatostatin was only slightly elevated above pre-infusion levels. 5. Compared with the effects of infusing HCl, infusions of emulsified butterfat or hyperosmolar NaCl and sucrose induced a greater intensity of antral motor activity and faster outflow of gastric effluent, although not to the same extent as with isotonic NaHCO3. However, as with isotonic NaHCO3, these infusates did not evoke the release of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutrient sensitivity of gastric emptying of digesta in the preruminant calf. 289 16

Transport of electrolytes, particularly of Cl- and K+, by the rat proximal colon was studied in vivo under conditions of high and low K+ diet and in the presence of transport inhibitors and secretagogues. The electrical parameters, PD, Isc, Rm, were monitored by direct clamping and via cable analysis. The present work reinforces own earlier work and that of others that - under control conditions - absorption of Na+ and Cl- is mainly electrically neutral. Low K+ diet reduced absorption of Na+ and Cl-, as well as secretion of K+, and increased HCO3- absorption. High K+ predominantly increased K+ secretion and reduced HCO3- absorption, these diet-induced changes being electrically neutral. Secretagogues such as PGE1 and theophylline reduced net absorption of Na+ and Cl-, increased the Isc and lowered the Rm. These effects could be reversed by the antidiarrheal drugs, loperamide and somatostatin, except the increase of K+ secretion, and reversed HCO3- transport absorption to secretion. A model consisting of absorptive columnar cells and secreting crypt cells is presented which encompasses the known and supposed aspects of colonic ion transport.
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PMID:Modelling of colonic Cl- and K+ transport under resting and secreting conditions. 382 67

Luminal application of acid was recently shown to stimulate surface epithelial HCO3(-) transport in stomach and duodenum. Effects of some potential transmitters of this response were therefore studied in amphibian gastric fundic and proximal duodenal mucosa in vitro. Duodenal HCO3- transport, which could be titrated directly, was stimulated by dibutyryl cAMP (DBcAMP, 10(-6) M), the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-6) M), noradrenaline (10(-6) M), pancreatic glucagon (10(-8) M), and gastric inhibitory peptide (GIP, 10(-10) M). Stimulation by glucagon, but not by prostaglandin E2 (PGE2, 10(-6) M), required Cl- in the luminal solution and was prevented by furosemide (10(-3) M). This suggests that glucagon may affect HCO3(-)-Cl- exchange at the luminal membrane while transport stimulated by prostaglandins may be electrogenic. Stimulatory effects of glucagon and PGE2 were also additive. Gastric HCO3- transport, studied in tissues after inhibition of H+ secretion by histamine H2-antagonists, clearly differed from duodenum in that noradrenaline and GIP were inhibitory and DBcAMP was without effect. Stimulation of gastric HCO3- transport was observed with glucagon (10(-8) M), natural cholecystokinin (CCK, 10(-8) M), and CCK octapeptide (10(-7) M), CCK preparations had no effect in the duodenum. Although tested over a wide range of concentrations, no effect on either duodenal or gastric HCO3- transport was observed with histamine, pentagastrin, tetragastrin, urogastrone, ACTH, bombesin, motilin, secretin, serotonin, somatostatin, substance P, or vasoactive intestinal peptide.
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PMID:Gastric and duodenal HCO3- transport in vitro: effects of hormones and local transmitters. 697 77

The effect of somatostatin 28, a noval intestinal peptide containing somatostatin in its C-terminal portion, was tested on basal exocrine pancreatic secretion on conscious dogs and after stimulation by secretin (1 CU x kg-1 x hr-1), caerulein (37.5 ng x kg-1 x hr-1) or secretin (2 CU x kg-1 x hr-1) caerulein (37.5 ng x kg-1 x hr-1). We found differences in the inhibitory effect of somatostatin 28 on these three forms of stimulation. Bicarbonate secretion stimulated by secretin was inhibited only slightly by large doses of somatostatin 28, whereas small doses markedly inhibited stimulation by caerulein. Protein concentrations were inhibited only when secretin was the stimulant. Protein outputs to all forms of stimulation were inhibited. When compared with synthetic somatostatin 14, lower doses of somatostatin 28 were required to produce the same inhibitory effect on protein outputs stimulated by secretin alone and on volumes stimulated by caerulein alone.
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PMID:Somatostatin 28: effects on exocrine pancreatic secretion in conscious dogs. 740 90

The role of somatostatin-14 in duodenal mucosal HCO3- secretion was investigated in anesthetized, indomethacin-treated guinea pigs. Net HCO3- output from the isolated, perfused (24 mM NaHCO3 + 130 mM NaCl) proximal duodenum was measured during intravenous infusion (alone or in combination) of somatostatin-14, carbachol, vasoactive intestinal peptide (VIP), and prostaglandin E2 (PGE2). In homogenates of duodenal enterocytes, the effect of these agents on adenylate cyclase activity was studied. Basal duodenal HCO3- secretion (3.5 +/- 0.2 mumol/cm/10 min) was reduced dose dependently by somatostatin-14 (10(-11) mol/kg, 10(-9) mol/kg, and 10(-7) mol/kg). Carbachol, VIP, and PGE2 (all 10(-8) mol/kg) increased basal duodenal HCO3- secretion two- to threefold. Somatostatin-14 (10(-7) mol/kg) abolished the stimulatory effect of carbachol and VIP, but not that of PGE2. Basal adenylate cyclase activity in isolated duodenal enterocytes (9.4 +/- 1.0 pmol cAMP/mg protein/min) was unaltered by somatostatin (10(-6) mol/liter) or carbachol (10(-3) mol/liter). VIP (10(-8) mol/liter) and PGE2 (10(-7) mol/liter) increased adenylate cyclase activity two- to threefold, and these effects were unchanged by somatostatin-14 (10(-6) mol/liter). In conclusion, somatostatin-14 inhibits basal and carbachol- and VIP-stimulated duodenal HCO3- secretion, and its mechanism of action is not via inhibition of adenylate cyclase activity in duodenal enterocytes.
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PMID:Effect of somatostatin-14 on duodenal mucosal bicarbonate secretion in guinea pigs. 789 65

In guinea-pig gallbladder epithelium, cAMP converts electroneutral HCO3- secretion into an electrogenic process. The effects of blood side Ba2+ (5 mmol/l) on HCO3- transport were investigated in vitro, using pH-stat and voltage clamp techniques to determine unidirectional fluxes of HCO3- and transepithelial electrical characteristics. Serosal, not mucosal addition of Ba2+ elevated short-circuit current (Isc), transepithelial potential difference, and tissue conductance; it inhibited the absorptive HCO3- flux while leaving the secretory flux unchanged. The Isc effect of Ba2+ was inhibited or prevented by tetrodotoxin; D- and L-propranolol; the Cl- channel blocker 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; the intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)ocytl ester; noradrenaline, by a yohimbine-sensitive action; somatostatin; HCO3(-)-free solutions. Thus Ba2+ appeared to release a neurotransmitter that gives rise to cAMP synthesis sufficient to turn part of electroneutral HCO3- secretion electrogenic. In a search for the involved signalling pathways, the H1-receptor antagonist, cetirizine, largely and hexamethonium, atropine, atenolol, indomethacin, and trifluoperazine entirely failed to antagonize the Isc effect of Ba2+. Similarly, carbachol, dobutamine, salbutamol, and serotonin were unable to mimic the action of Ba2+ and Isc effects of histamine were small and short-lived. By contrast, vasoactive intestinal peptide (VIP; 3 x 10(-7) mol/l) completely transformed HCO3- secretion into an electrogenic process. The VIP receptor antagonist (4Cl-DPhe6, Leu17) VIP, delayed and reduced the Isc responses to Ba2+ and VIP. As guinea-pig gallbladder epithelial cells possess cAMP-coupled VIP receptors close to VIPergic neurons, Ba2+ is likely to act by releasing VIP from neural terminals.
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PMID:Electrogenic bicarbonate secretion in gallbladder: induction by barium via neuronal, possibly VIP-ergic pathways. 790 68

Somatostatin (10(-10)-10(-7) mol/l) caused a concentration-dependent increase of the diameter of isolated crypts from the rat distal colon. Cell swelling was restricted to the upper one-third of the crypt and was dependent on the presence of Na+ and Cl- ions, indicating that it was caused by the stimulation of NaCl absorption by the hormone. Swelling was followed by a regulatory volume decrease, which could be inhibited by K+ and Cl- channel blockers. Also a lipoxygenase inhibitor and a leukotriene D4 receptor blocker inhibited volume regulation. Whole cell recordings performed in parallel revealed that somatostatin induced a depolarization of the cells at the upper one-third of the crypt but had no effect in the deeper parts of the crypt. This depolarization was concomitant with an increase in Cl- (and partially also HCO3-) conductance and was suppressed by a leukotriene D4 receptor blocker. In contrast, when Cl- secretion was stimulated by vasoactive intestinal peptide, a secretagogue acting on the adenosine 3',5'-cyclic monophosphate (cAMP) pathway, the effect of somatostatin was reversed from a depolarization into a hyperpolarization, an effect that was also observed in deeper parts of the crypt. Consequently, in crypts stimulated via the cAMP pathway, somatostatin inhibits the activation of apical Cl- channels. Somatostatin also partially inhibited the increase of K+ conductance induced by carbachol, a secretagogue acting on the Ca2+ pathway. Ussing chamber experiments showed that somatostatin caused a concentration-dependent decrease of short-circuit current. This decrease was dependent on the presence of Cl- and HCO3- ions. Measurements of unidirectional ion fluxes indicated that somatostatin stimulated Cl- absorption by an increase of the mucosa-to-serosa flux of this ion. The stimulation of Cl- absorption was completely suppressed by a Cl- channel blocker and by a lipoxygenase inhibitor. Consequently, the activation of a volume/leukotriene-sensitive basolateral Cl- conductance seems to be involved in the stimulation of Cl- absorption by somatostatin.
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PMID:Effect of somatostatin on cell volume, Cl- currents, and transepithelial Cl- transport in rat distal colon. 791 93


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