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)

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

The effect of a synthetic somatostatin analog was studied in a patient with severe secretory diarrhea due to pancreatic cholera syndrome. Basal intestinal perfusion studies indicated an absence of water and sodium absorption, and active chloride secretion in the small bowel. Intravenous administration of the somatostatin analog (1 microgram/kg.h) changed zero net water movement to absorption (122 mL/30 cm of the jejunum per hour). Chloride secretion changed to absorption (5.0 to 7.9 meq/30 cm.h), and plasma vasoactive intestinal polypeptide concentration was reduced from 330 to 45 pmol/L (normal, less than 51). When the analog was given subcutaneously, 100 micrograms twice daily, stool weight decreased, and plasma vasoactive intestinal polypeptide concentration fell toward the normal range (67 pmol/L). Plasma concentration of pancreatic polypeptide was initially elevated and dropped during intravenous infusion of somatostatin analog but returned to baseline on maintenance therapy with the analog delivered subcutaneously. The patient has not had further diarrhea during 9 months of therapy.
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PMID:Pancreatic cholera syndrome: effect of a synthetic somatostatin analog on intestinal water and ion transport. 286 21

The effects of opioids on transepithelial potential difference and short-circuit current across guinea pig ileum stripped of one muscle layer were measured in vitro in Ussing chambers. Opioid peptides such as [DAla2, DLeu5]enkephalin and [DAla2, DMet5]enkephalin, which are primarily agonists at delta-opiate receptors, were able to reduce transepithelial potential difference and short-circuit current at concentrations as low as 1 nM. The narcotic drug etorphine was also very potent in reducing short-circuit current, but fentanyl and morphine, which are primarily agonists at mu-opiate receptors, were almost completely ineffective. Ketocyclazocine was relatively ineffective, and beta-endorphin had intermediate potency. All opioid effects could be reversed by the opiate antagonist naloxone. Somatostatin also reduced short-circuit current, but its effect was not reduced by naloxone. Chloride flux measurements indicated that the effect of etorphine on short-circuit current is associated with an enhancement of active Cl- absorption. The relative effects of opioids in this system suggest that their actions are being mediated by a specific delta-opiate receptor. In contrast, opioid effects on guinea pig intestinal smooth muscle seem to be primarily mediated by a mu-opiate receptor.
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PMID:Control of guinea pig intestinal electrolyte secretion by a delta-opiate receptor. 624 64

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

Somatostatin (SST) is a peptide hormone comprising 14 or 28 amino acids that inhibits endocrine and exocrine secretion via five distinct G-protein-coupled receptors (SSTR1-5). SSTR5 has an important role in inhibiting the secretion of pancreatic and gastrointestinal hormones (e.g., insulin, GLP-1, PYY) through the binding of SSTs; hence, SSTR5 antagonists are expected to be novel anti-diabetic drugs. In the course of our lead generation program of SSTR5 antagonists, we have discovered a novel spiroazetidine derivative 3a. However, pharmacological evaluation of 3a revealed that it had to be administered at a high dose (100mg/kg) to show a persistent glucose-lowering effect in an oral glucose tolerance test (OGTT). We therefore initiated an optimization study based on 3a aimed at improving the antagonistic activity and mean residence time (MRT), resulting in the identification of 2-cyclopropyl-5-methoxybiphenyl derivative 3k. However, 3k did not show a sufficient persistent glucose-lowering effect in an OGTT; moreover, hERG inhibition was observed. Hence, further optimization study of the biphenyl moiety of compound 3k, focused on improving the pharmacokinetic (PK) profile and hERG inhibition, was conducted. Consequently, the introduction of a chlorine atom at the 6-position on the biphenyl moiety addressed a putative metabolic soft spot and increased the dihedral angle of the biphenyl moiety, leading to the discovery of 3p with an improved PK profile and hERG inhibition. Furthermore, 3p successfully exhibited a persistent glucose-lowering effect in an OGTT at a dose of 3mg/kg.
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PMID:Discovery of novel somatostatin receptor subtype 5 (SSTR5) antagonists: Pharmacological studies and design to improve pharmacokinetic profiles and human Ether-a-go-go-related gene (hERG) inhibition. 2862 5