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 and its analogs have been shown to inhibit both pancreatic endocrine and exocrine function. We hypothesized that octreotide acetate (Sandostatin), a somatostatin analog, decreases the pancreatic flow rate through a peptide-mediated mechanism and alters pancreatic fluid composition by inhibiting carbonic anhydrase action and circulating peptide levels. To test this hypothesis, we collected pancreatic fluid from six patients (four with pancreatic fistulas and two with pancreatic drains after pancreatic resection). Pancreatic fluid volume and chloride, sodium, potassium, amylase, lipase, and bicarbonate levels were measured before and after octreotide acetate therapy. Octreotide acetate reduced pancreatic fluid output by a mean of 75 percent (p less than 0.05), increased chloride concentration by 21 percent (p less than 0.05), and reduced bicarbonate content by 45 percent (p less than 0.05). Sodium levels were unchanged, but the potassium concentration was increased by 14 percent (p less than 0.05). Total amylase and lipase production per 24 hours was decreased by 63 percent and 27 percent, respectively (differences not significant). Somatostatin may be useful in the treatment of established pancreatic fistulas and may be a useful prophylactic tool to prevent postoperative fistula formation.
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PMID:Effect of octreotide acetate on pancreatic exocrine function. 246 37

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

Ten male healthy volunteers were studied in order to determine whether the synthetic somatostatin analogue Sandostatin (SMS 201-995) has effects similar to those of natural somatostatin on renal water and electrolyte excretion. The study was carried out in three separate placebo-controlled randomized double-blind cross-over trials. The subjects received single sc injections of 100 micrograms Sandostatin and placebo under conditions of mild diuresis (trial 1), water load with enhanced diuresis (trial 2), and water load with exogenous lysin-vasopressin (5 IU sc) induced antidiuresis (trial 3). The following parameters were measured: urine flow rate, serum and urine osmolalities, osmolar clearance, free water and creatinine clearances, excretion rates of sodium, potassium, calcium, chloride, and phosphate, and immunoreactive insulin. A marked antidiuretic effect was observed within 2 h after dosing in all three trials. Urine flow rates were reduced by 45% in trial 1 and by 29 and 31% in trials 2 and 3, respectively (all P less than 0.05). There were no differences in effects on serum and urine osmolalities between Sandostatin and placebo. Osmolar clearance was significantly reduced in trial 1 (P less than 0.01). Free water clearance significantly decreased only in trial 2 (P less than 0.05). Sodium excretion decreased by 49, 48 and 67%, respectively, the differences being significant in trials 1 and 3 (P less than 0.05). Calcium excretion decreased by 66, 70 and 54% (all P less than 0.001). Chloride excretion decreased by 28, 22 and 44%, the differences being significant in trials 2 and 3 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antidiuretic effect of Sandostatin (SMS 201-995) in healthy volunteers. 265 54

Adrenocortical somatostatin receptors have been shown to interact with somatostatin-14 (S-14) and somatostatin-28 (S-28). To determine whether these peptides interact with the same or different receptor proteins, we chemically cross-linked these receptors using disuccinimidyl suberate to radioligands prepared from tyrosinated S-14 and S-28 analogs. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and subsequent autoradiography of [125I-Tyr11] S-14 and [Leu8, D-Trp22, 125I-Tyr25] S-28 cross-linked to their binding sites following solubilization in the presence of 50 mM DTT revealed the presence of a single labelled protein of Mr = 200,000. When the cross-linked material was treated under non-reducing conditions, this band was not observed. Furthermore, addition of excess S-14 and S-28 at the time of binding inhibited the incorporation of both radioligands into the receptor protein. These results demonstrate that adrenocortical membrane receptors for somatostatin contain a single receptor protein sub-unit or sub-units of identical size which interact with both S-14 and S-28.
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PMID:Chemical cross-linking of somatostatin receptors in rat adrenal cortex. 287 6

Intestinal epithelium absorbs calcium by an energy-dependent cellular process that is stimulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Calcium entry across the brush border is driven by existing electrochemical gradients; exit across the basolateral membrane against these same gradients is driven by a calcium-activated ATPase, sodium-calcium exchange, or both. The specific cellular sites of 1,25(OH)2D3 action remain to be identified. Calcium transport is independent of phosphate and influenced by sodium. Sodium may alter calcium transport at the brush border through alterations of the transmembrane electrical gradient and at the basolateral membrane by exchange with intracellular calcium. The segmental distribution of calcium active transport is heterogeneous, with maximal flux rates in the proximal portions of small intestine and colon and net secretion in mid- and distal small intestine and mid- and distal colon. 1,25(OH)2D3 converts regions of net secretion in ileum and colon to net absorption. 1,25(OH)2D3-stimulated active phosphate transport is largely confined to areas of low-calcium transport, with maximal phosphate absorption in jejunum, the site of maximal calcium secretion. Calcium secretion, primarily in jejunum and ileum, is nonsaturable, may follow the paracellular pathway, and is stimulated by mucosal sodium and somatostatin.
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PMID:Factors that influence absorption and secretion of calcium in the small intestine and colon. 388 91

The effect of low concentrations of sodium taurocholate on the secretory and electrical activity of isolated rabbit fundic mucosa has been studied. Fundic mucosa maintained a stable potential difference (10.2 +/- 0.6 mV, n = 70) and electrical resistance (85 +/- 6 omega . cm-2, n = 70) and the majority of preparations spontaneously secreted acid (2.85 +/- 0.31 mumol . cm-2 . h-1, n = 70). Histamine (10(-5) and 10(-4) M) and carbachol (10-4 M) increased acid secretion, and these responses were prevented by cimetidine (10(-3) M) and atropine (10(-5) M), respectively. Mucosal application of taurocholate (10(-4) and 10(-3) M) increased net acidity without altering electrical activity. This response exhibited tachyphylaxis, was not altered by pretreating the tissues with cimetidine (10(-3) M), atropine (10(-5) M), or somatostatin (10(-6) M), and occurred in mucosas maximally stimulated by histamine. Sodium thiocyanate (6 x 10(-2) M, serosal side) inhibited spontaneous acid secretion revealing net alkalinization (0.83 +/- 0.05 mumol . cm-2 . h-1, n = 58) that was completely inhibited by anoxia and potassium cyanide (10(-2) M) and markedly reduced by 2,4-dinitrophenol (10(-4) M). Some fundic preparations spontaneously secreted alkali (1.20 +/- 0.20 mumol . cm-2 . h-1, n = 6) after an initial period of acid secretion. Mucosal-side taurocholate (10(-3) M) converted net alkali secretion by both thiocyanate-treated and spontaneously-secreting mucosas to acid secretion without affecting electrical conductance. These secretory responses may be implicated in the pathogenesis of gastric mucosal damage by bile salts.
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PMID:Studies of acid and alkaline secretion by rabbit gastric fundus in vitro: effect of low concentrations of sodium taurocholate. 612 66

Teleost fish osmoregulation is largely the result of integrated transport activities of the gill, gut and renal system. The basic 'epithelial fabric' in each of these tissues is adapted to provide the appropriate transport mechanisms depending upon whether the fish is in fresh water or sea water. Net NaCl transport by the branchial epithelium reverses direction when euryhaline species migrate between the two media, providing a useful focus in experiments designed to elucidate mechanisms of differentiation and integration of transport function. Isolated opercular membranes and skins from certain seawater-adapted species are good models to study branchial salt extrusion mechanisms. These heterogeneous tissues generate short-circuit currents equal to net chloride secretion. The vibrating probe technique has allowed localization of all current and almost all conductance to the apical crypt of chloride cells. Area-specific surface current and conductance of chloride cells are 18 mA cm-2 and 580 mS cm-2 (1.7 omega cm2), ranking them as one of the most actively transporting and conductive cells known. There is no net sodium transport under short-circuit conditions but the chloride secretion process is sodium-dependent and ouabain and 'loop'-diuretic sensitive. Sodium fluxes through chloride cells are large (PNa = 5.2 X 10(-4) cms-1) nd appear passive and rate-limited by a single barrier. A link may exist between the active transport and leak pathways since sodium fluxes always account for 50% of chloride cell conductance. The sodium pathway is probably the chloride cell-accessory cell tight junction, although this is still unresolved. Chloride secretion can be rapidly modulated by several hormones, including catecholamines, somatostatin, glucagon, vasoactive intestinal polypeptide and urotensins I and II. Regulation by these hormones may be by rapid alterations of cellular cAMP levels. Differentiation of chloride cells and chloride secretion may be controlled by cortisol and prolactin. Cortisol stimulates chloride cell proliferation and differentiation and appears to interact with NaCl to initiate salt secretion. Prolactin appears to cause chloride cell dedifferentiation by reducing both the active-transport and leak pathways proportionately.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chloride cells and the hormonal control of teleost fish osmoregulation. 636 Dec 7

Sodium ions have been shown to reduce the binding of agonists to a number of G protein-linked receptors. They are believed to do so by interacting with aspartate residues in the second membrane-spanning region of these receptors to cause G protein uncoupling, resulting in a diminished affinity of the receptors for agonists. To investigate Na+ regulation of agonist binding to somatostatin receptors, Na+ was tested for its effect on the binding of agonists to cloned somatostatin receptor type 1 (SSTR1) and somatostatin receptor type 2 (SSTR2) stably expressed in Chinese hamster ovary cells. Na+ reduced agonist binding to SSTR2 but not to SSTR1. Because high affinity agonist binding to SSTR1 does not depend on G protein coupling but agonist binding to SSTR2 is reduced by guanosine-5'-(beta, gamma-imido)triphosphate and pertussis toxin treatment, the selective Na+ effect on SSTR2 is consistent with previous findings with other receptors showing that Na+ uncouples receptors from G proteins, thereby reducing the affinity of the receptors for agonists. Conversion of Asp89 to Asn89 in SSTR2 resulted in a mutant receptor whose affinity for agonists was not altered by Na+, indicating that Asp89 is involved in mediating the effects of Na+ on agonist binding to SSTR2. However, the affinities of the mutant and wild-type receptors for somatostatin were the same, and both guanosine-5'-O-(gamma-thio)triphosphate and pertussis toxin treatment reduced agonist binding to the mutant and wild-type receptors. These findings differ from the results of similar mutagenesis studies on other G protein-linked receptors, in that the mutant and wild-type SSTR2 forms associate with G proteins in similar ways. These results indicate that Asp89 acts in a novel manner to regulate agonist binding and G protein interaction with SSTR2.
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PMID:Mutation of an aspartate at residue 89 in somatostatin receptor subtype 2 prevents Na+ regulation of agonist binding but does not alter receptor-G protein association. 810 84

The biosynthesis of aldosterone in the adrenal zona glomerulosa is influenced by a number of factors of which the main physiological regulator is the octapeptide, angiotensin II (AII). Sodium restriction increases plasma aldosterone, adrenal glomerulosa AII receptors and the activity of enzymes of the early and late aldosterone biosynthetic pathway. The effects of sodium restriction are mimicked by prolonged administration of low doses of AII, and prevented by blockade of AII formation using converting enzyme inhibitors, indicating that the effects of sodium restriction are mediated by AII. However, the adrenal glomerulotrophic actions of AII are impaired in rats on high sodium diet indicating that other factors are modulating the effects of AII in these conditions. A number of factors are known to influence aldosterone secretion, several of which have been shown to preferentially modulate the effect of AII. While the stimulatory effect of AII is potentiated by serotonin or increases in extracellular potassium, it is inhibited by dopamine, somatostatin and atrial natriuretic peptide. Future investigations will be important to understand the relative role of the individual regulators in the physiological control of adrenal sensitivity to AII, and how activation of various intracellular messenger systems results in changes in activity of the enzymes of the aldosterone biosynthetic pathway.
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PMID:Factors controlling steroid biosynthesis in the zona glomerulosa of the adrenal. 848 39

Duodenal fat such as oleate is known to influence gut functions by release of cholecystokinin (CCK), but the contribution of CCK endogenously released by duodenal fat or by diversion of pancreatic juice from the duodenum in the mechanism of mucosal integrity and gastroprotection has been little studied. This study was designed to compare the effect of CCK-8 and intraduodenal (i.d.) instillation of sodium oleate, or diversion of the pancreatic biliary secretions that are known to release CCK, on the gastric mucosal lesions induced by topical application of 100% ethanol or acidified aspirin (ASA) in rats with or without the pretreatment with a CCK-A receptor antagonist, loxiglumide, or with L-365,260 to block CCK-B receptors. In addition, the effect of suppression of prostaglandin (PG) biosynthesis by indomethacin (5 mg/kg i.p.), inhibition of nitric oxide (NO)-synthase by L-NAME (5 mg/kg i.v.), or blockade of sensory nerves by capsaicin (125 mg/kg s.c.) on the protective activity of sodium oleate was determined. Sodium oleate (50-200 mM i.d.), or diversion of pancreatic juice from the duodenum for 3 h that produced significant rise in plasma CCK levels, significantly reduced gastric lesions induced by 100% ethanol to an extent similar to that induced by exogenous CCK-8 (5 nmol/kg s.c.). The protective effect of oleate or diversion of pancreatic juice was accompanied by an increase in gastric blood flow (GBF). Both protection and accompanying hyperemia were completely abolished by blockade of CCK-A receptors with loxiglumide, whereas L-365,260, an antagonist of CCK-B receptors, had no effect. Oleate given i.d. significantly attenuated acidified ASA-induced gastric lesions and gastric secretion while increasing the luminal concentration of somatostatin. These effects were significantly reduced by loxiglumide but not by L-365,260. In contrast, CCK-8, which stimulated gastric acid secretion, failed to affect the lesions induced by acidified ASA and the decrease in the GBF produced by this ulcerogen. Indomethacin, which suppressed PG generation by approximately 90%, failed to influence the protective activity of oleate or CCK-8 against ethanol-induced lesions, whereas L-NAME, vagotomy, or sensory denervation significantly attenuated this protection and accompanying hyperemia. Addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK-8 and duodenal oleate against gastric lesions induced by ethanol or acidified ASA. We conclude that endogenous CCK released by oleate or diversion of pancreatic secretion exerts a potent gastroprotective action on the stomach involving predominantly CCK-A receptors and depending on vagal activity, and hyperemia mediated by NO and sensory nerves but unrelated to acid secretory effects and endogenous PG.
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PMID:Involvement of endogenous cholecystokinin and somatostatin in gastroprotection induced by intraduodenal fat. 987 9


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