Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous in vivo studies showed that systemic ethanol enhanced hippocampal neuronal responses to iontophoretically applied acetylcholine and somatostatin while having little or no effect on responses to other transmitters. We previously reported that these two agonists reciprocally regulate the non-inactivating, voltage-dependent K+ current called the M-current. Therefore, we tested ethanol superfusion on this current in rat hippocampal pyramidal neurons in vitro, using intracellular recording and single electrode voltage-clamp methods. Tetrodotoxin (TTX) was used to block Na+ spikes and synaptic transmitter release. Ethanol in low concentrations (22-44 mM), like muscarinic agonists, greatly reduced the M-current amplitude at depolarized membrane potentials and at 44 mM antagonized its augmentation by somatostatin. These changes were often accompanied by an inward baseline current with a conductance decrease. Other than a small inward current in some cells there was little or no consistent ethanol effect at resting membrane potentials. Atropine 1 microM (and TTX) did not alter the ethanol effect on the M-current. Therefore, the site of ethanol action is most likely distal to the muscarinic receptor. Ethanol reduction of the M-current, by summation of like effects, may account for the potentiation of acetylcholine responses seen in vivo and in vitro, and provides a mechanism for the excitatory effects of ethanol on some central neurons.
 ...
PMID:Ethanol diminishes a voltage-dependent K+ current, the M-current, in CA1 hippocampal pyramidal neurons in vitro. 197 65

The ability of ketone bodies to suppress elevated hepatic glucose output was investigated in eight postabsorptive subjects with non-insulin-dependent diabetes mellitus (NIDDM). Infusion of sodium acetoacetate alone (20 mumols/kg/min) for 3 hours increased total serum ketones (beta-hydroxybutyrate and acetoacetate) to approximately 6 mmol/L, but did not reduce plasma glucose (14.0 +/- 0.8 to 12.3 +/- 0.9 mmol/L) or isotopically determined hepatic glucose output (17.5 +/- 1.4 to 12.7 +/- 1.0 mumols/kg/min) more than saline alone. Plasma C-peptide concentrations were unchanged, while serum glucagon increased from 131 +/- 13 to 169 +/- 24 ng/mL (P less than .015) and free fatty acids were suppressed by 43% (0.35 +/- 0.08 to 0.20 +/- 0.06 mmol/L, P less than .025). When sodium acetoacetate was infused with somatostatin (0.10 micrograms/kg/min) to suppress glucagon and insulin secretion, the decrease in both plasma glucose (13.3 +/- 0.9 to 10.2 +/- 0.7 mmol/L) and hepatic glucose output (17.2 +/- 1.6 to 9.4 +/- 0.6 mumols/kg/min) was greater than either acetoacetate or somatostatin infusion alone. Infusion of equimolar amounts of sodium bicarbonate had no effect on glucose metabolism. In conclusion, these results demonstrate that ketone bodies can directly suppress elevated hepatic glucose output in NIDDM independent of changes in insulin secretion, but only when the concomitant stimulation of glucagon secretion is prevented. Ketone bodies also suppress adipose tissue lipolysis in the absence of changes in plasma insulin and may serve to regulate their own production.
 ...
PMID:Effects of ketone bodies on carbohydrate metabolism in non-insulin-dependent (type II) diabetes mellitus. 197 25

We have investigated the effect of the addition of somatostatin and trimetaphan to sufentanil 20 micrograms kg-1 on the hormonal responses to cardiac surgery and compared the changes with a control group receiving sufentanil and sodium nitroprusside. Eighteen patients undergoing elective valve replacement surgery were studied. Patients who received somatostatin and trimetaphan in addition to sufentanil had significantly smaller serum growth hormone and plasma glucagon concentrations compared with those who received sufentanil and sodium nitroprusside. The cortisol response to surgery was inhibited in both groups. There were no significant differences in catecholamine concentrations between the two groups. There was no effect of the additional inhibition of glucagon and growth hormone on circulating concentrations of glucose and lactate, but plasma concentrations of non-esterified fatty acids increased significantly. Thus the addition of somatostatin increased the suppression of the hormonal response to cardiac surgery by sufentanil.
 ...
PMID:Hormonal responses to cardiac surgery: effects of sufentanil, somatostatin and ganglion block. 197 42

The caudal neurosecretory peptide urotensin II and its partial structural analog the hypothalamic and gastroenteropancreatic peptide somatostatin can be distinguished by the goby posterior intestine; urotensin II stimulates Na+ and Cl- absorption whereas somatostatin is without effect. Sandostatin (Sandoz compound SMS 201-995) is a partial structural analog of somatostatin, possessing the active core common to both urotensin II and somatostatin but lacking the C- and N-terminal tails which apparently confer recognition in species specificity. SMS 201-995 mimicked the effects of urotensin II, namely, increased net Cl- absorption and decreased radiochloride backflux consistent with the observed increase in transepithelial resistance and the cellular depolarization typical of transport stimulation in this tissue. Speculation on the role of the tails in species-specific recognition is supported by the nature of amino acid residue substitutions in urotensin II, somatostatin, and SMS 201-995 and suggests the existence of multiple receptor types for this group of peptides.
 ...
PMID:Recognition by goby intestine of a somatostatin analog, SMS 201-995. 197 1

We have synthesized two photoreactive derivatives of somatostatin, namely [125I-Tyr11,azidonitrobenzoyl (ANB)-Lys4]somatostatin and [125I-Tyr11,ANB-Lys9]somatostatin, and used them to characterize somatostatin receptors biochemically in several cell types. Saturation binding experiments carried out in the dark demonstrated that [125I-Tyr11,ANB-Lys4]somatostatin bound with high affinity (KD = 126 +/- 39 pM) to a single class of binding sites in GH4C1 pituitary cell membranes. The affinity of this analog was similar to that of the unsubstituted peptide [125I-Tyr11]somatostatin (207 +/- 3 pM). In contrast, specific binding was not observed with [125I-Tyr11,ANB-Lys9]somatostatin. The binding of both [125I-Tyr11,ANB-Lys4]somatostatin and [125I-Tyr11]somatostatin was potently inhibited by somatostatin (EC50 = 300 pM) whereas at 100 nM unrelated peptides had no effect. Furthermore, both pertussis toxin treatment and guanyl-5'yl imidophosphate (Gpp(NH)p) markedly reduced [125I-Tyr11,ANB-Lys4]somatostatin binding. Thus, [125I-Tyr11,ANB-Lys4]somatostatin binds to G-protein coupled somatostatin receptors with high affinity. To characterize these receptors biochemically, GH4C1 cell membranes were irradiated with ultraviolet light following the binding incubation, and the labeled proteins were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. A major band of 85 kDa was specifically labeled with [125I-Tyr11,ANB-Lys4]somatostatin but not with [125I-Tyr11,ANB-Lys9]somatostatin or [125I-Tyr11]somatostatin. The binding affinity of the 85-kDa protein for [125I-Tyr11,ANB-Lys4]somatostatin was very high (Kd = 34 pM). Labeling of this protein was inhibited competitively by somatostatin (EC50 = 140 +/- 80 pM) but not by unrelated peptides. Furthermore, this band was not labeled in pertussis toxin-treated membranes or in untreated membranes incubated with Gpp(NH)p. Finally, [125I-Tyr11,ANB-Lys4]somatostatin specifically labeled bands of 82, 75, and 72 kDa in membranes prepared from mouse pituitary AtT-20 cells, rat pancreatic acinar AR4-2J cells, and HIT hamster islet cells, respectively. Thus, [125I-Tyr11,ANB-Lys4]somatostatin represents the first photolabile somatostatin analog able to bind to receptors with high affinity. Our studies demonstrate that this novel peptide covalently labels specific somatostatin receptors in a variety of target cell types.
 ...
PMID:Identification of somatostatin receptors by covalent labeling with a novel photoreactive somatostatin analog. 197 33

To determine whether biosynthesis of somatostatin is enhanced in the primary sensory neurons by inflammatory pain, we examined the effects of adjuvant inoculation on the content of immunoreactive somatostatin, mainly composed of somatostatin-14 and somatostatin-28, in the dorsal root ganglia and the spinal cord of the rat. The adjuvant inoculation, which produced long-lasting inflammation and hyperalgesia, increased the content of immunoreactive somatostatin, especially somatostatin-14, in the dorsal root ganglia at L4-L6 levels with no change in the dorsal and ventral horns of lumbar enlargement. Such an increase was enhanced by an intrathecal injection of colchicine (0.2 mg) that inhibits axonal flow of somatostatin. Chronic administration of the anti-inflammatory analgesic, sodium diclofenac (3 mg.kg-1.d-1), abolished an adjuvant-induced increase in the content of immunoreactive somatostatin in the dorsal root ganglia. These results suggest that the turnover (biosynthesis and axonal flow) of somatostatin in the primary sensory neurons is enhanced in the presence of persisting inflammatory pain, and support the idea that somatostatin-containing primary afferents are involved in the transmission of pain in the spinal dorsal horn.
 ...
PMID:Somatostatin is increased in the dorsal root ganglia of adjuvant-inflamed rat. 197 11

In 13 men with chronic duodenal ulcer disease effects of somatostatin and naloxone on basic gastric secretion were determined. Following intravenous somatostatin infusion a significant increase in basic gastric secretion was observed. Somatostatin also induced a significant increase in sodium concentration and a decrease in chloride concentration in the gastric juice. Total electrolyte and mucoprotein secretions changed proportionally to alterations in the gastric juice volume. Somatostatin-induced gastric secretion was unaffected by a single intravenous naloxone administration. In patients with chronic duodenal ulcer disease somatostatin and naloxone affect gastric secretion independently of each other.
 ...
PMID:[Effect of naloxone on basal, by somatostatin inhibited stomach secretion in patients with chronic duodenal ulcer]. 197 11

To study the modulatory effects of somatostatin on membrane K+ currents, whole cell voltage-clamp recordings were performed on identified rat somatotrophs in primary culture. In the presence of Co2+ (2 mM) and tetrodotoxin (1 microM) in the bath solution to block Ca2+ and Na+ inward currents, two types of voltage-activated K+ currents were identified on the basis of their kinetics and pharmacology. First, a delayed rectifier K+ current (IK) had a threshold of -20 mV, did not decay during voltage steps lasting 300 ms, and was markedly attenuated by extracellular application of tetraethylammonium (TEA, 10 mM). Second, a transient outward K+ current (IA) was activated at -40 mV (from a holding potential of -80 mV) and persisted despite the presence of TEA. This IA was blocked by 4-aminopyridine (2 mM). Somatostatin (10 nM) increased IK by 75% and IA by 45% without obvious effects on steady-state voltage dependency of activation or inactivation, and these effects were reversible. This increase in K+ currents may contribute in part to the inhibitory effect of somatostatin on growth hormone release.
 ...
PMID:Somatostatin increases voltage-dependent potassium currents in rat somatotrophs. 197 15

The prosomatostatin-derived peptides, somatostatin-14 and somatostatin-28, are believed to function as neurotransmitters or neuromodulators in the cerebral cortex. To investigate the molecular mechanisms by which these peptides induce their physiological effects in the cerebral cortex, we have examined the effects of somatostatin-14 and somatostatin-28 on voltage-dependent Ca2+ currents in rat neocortical neurons in culture. Ca2+ currents were recorded using whole-cell patch-clamp techniques under conditions in which K+ and Na+ currents were blocked. Ca2+ currents were induced by depolarization from the holding potential of -80 mV. Somatostatin-14 (100 nM) and somatostatin-28 (100 nM) did not significantly affect low-voltage activated Ca2+ currents, but blocked high-voltage activated Ca2+ currents and slowed the activation of this current. The effects of both peptides were concentration-dependent and reversible. Furthermore, the effects of somatostatin-14 and somatostatin-28 on the high-voltage activated Ca2+ currents were not additive, suggesting that both peptides regulate this ionic current through similar cellular mechanisms. When patch pipettes used to record the Ca2+ currents contained 100 microM cAMP and 0.5 mM isobutylmethylxanthine, a phosphodiesterase inhibitor, somatostatin-14 and somatostatin-28 still inhibited Ca2+ currents, indicating that the effects of these peptides on the Ca2+ currents were cAMP-independent. Inclusion of the non-hydrolysable guanine triphosphate analogue, guanine triphos-somatostatin-14 or somatostatin-28, suggesting the involvement of guanine nucleotide binding proteins in the actions of the peptides on the Ca2+ currents.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Somatostatin-14 and somatostatin-28 inhibit calcium currents in rat neocortical neurons. 197 53

In 41 patients, operated upon for common bile duct stones, a temporary bile fistula was achieved by means of a T-tube and a Foley-catheter with an occludable balloon. To learn more about peptide control of bile secretion, 6-8 days after surgery, bile flow was studied before as well as during infusion of the three peptides somatostatin, vasoactive intestinal peptide and secretin. The findings, also presented in Figure 17, were: 1. During somatostatin infusion, bile secretion decreased by 30%, and bile lipid output was reduced by some 10%. The clearance of [14C]-erythritol decreased by 25%, indicating an effect on the bile acid-dependent canalicular bile secretion (Paper I). 2. Vasoactive intestinal peptide (VIP) increased bile secretion by 65%. The concentration of bile lipids decreased, whereas the output was uneffected. The bicarbonate concentration increased, and the concentrations of sodium and potassium were uneffected. [14C]-erythritol clearance was not influenced by VIP infusion. Thus, VIP stimulated bile secretion at the ductular level (Paper II). 3. VIP increased bile secretion by 60%, whereupon secretin increased it by another 70%. Neither of the two peptides effected bile acid output. Both VIP and secretin increased bicarbonate output, whereas only VIP increased the concentration. The clearance of [14C]-erythritol was uneffected by VIP infusion, but increased following secretin, as did the clearance of [14C]-mannitol. Thus, VIP stimulated bile secretion at the ductular level, whereas secretin seemed to stimulate bile secretion both at the ductular level and at the bile acid non-dependent canalicular level (Paper III). 4. Whereas VIP stimulated bile secretion, somatostatin decreased it by some 40%. Even when somatostatin was administered during VIP infusion, no reduction of the VIP-induced choleresis was seen. VIP increased both bicarbonate concentration and output, whereas somatostatin had the opposite effect. The concentration of chloride increased following VIP infusion, but decreased following somatostatin. The output of bile acids was not influenced by VIP infusion and decreased by somatostatin, whereas total lipid concentration increased during somatostatin infusion with a decrease when VIP was added. Thus, somatostatin acts on the bile acid-dependent canalicular bile secretion and also, to some extent, on the ductular secretion. The effects of the two peptides on bile secretion are independent of each other (Paper IV). 5. While fasting, 6-8 days after bile duct surgery, bile secretion averaged 290 microliters/min. Canalicular bile secretion, as measured by the clearance of [14C]-erythritol, constituted some 80% of total bile flow. Maximum de novo synthesis of bile acids was 8.7 mmol/24 h, implying a 8-9 fold stimulation due to interrupted enterohepatic circulation (Paper V). 6. No serious side effects from this method with temporary bile fistulas following bile duct surgery were found. Therefore, the method is recommended for further research on human bile secretion (Paper V).
 ...
PMID:Bile secretion in man. The effects of somatostatin, vasoactive intestinal peptide and secretin. 198 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>