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)

The cellular mechanisms by which the hypothalamic peptide somatostatin (SRIF) inhibits Ca+(+) influx were investigated in the pituitary cell line AtT-20. Cytosolic Ca+(+) levels were measured using the fluorescent probe Quin 2. Calcium influx was stimulated by the Ca+(+) channel agonist Bay K 8644. Bay K 8644 increased Ca+(+) influx in a concentration-dependent manner and the stimulation of Ca+(+) influx was blocked by the Ca+(+) channel antagonists nifedipine and nitrendipine. SRIF analogs also blocked Bay K 8644-stimulated Ca+(+) influx. The rank order of potency of the analogs (SRIF-28 greater than D-Trp8-SRIF greater than SRIF) suggests that the effects of SRIF are mediated by SRIF-28 preferring receptors. Pretreatment of AtT-20 cells with pertussis toxin abolished SRIF's inhibition of Bay K 8644-evoked Ca+(+) influx suggesting that G proteins mediate the inhibitory effects of SRIF on Ca+(+) influx. The K+ channel antagonists tetraethylammonium, 4-aminopyridine and CsCl all stimulated Ca+(+) influx into AtT-20 cells. These agents did not alter Bay K 8644-evoked Ca+(+) influx or did they affect the ability of SRIF to inhibit Ca+(+) influx. Tetrodotoxin, the sodium channel blocker which inhibits action potential generation in AtT-20 cells, lowered basal Ca+(+) levels in AtT-20 cells but did not modify SRIF's inhibition of Bay K 8644-stimulated Ca+(+) influx. These findings suggest that SRIF receptors, linked directly to Ca+(+) channels via G proteins, may mediate SRIF's inhibition of Ca+(+) influx.
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PMID:Cellular mechanisms of somatostatin inhibition of calcium influx in the anterior pituitary cell line AtT-20. 169 31

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.
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PMID:Ethanol diminishes a voltage-dependent K+ current, the M-current, in CA1 hippocampal pyramidal neurons in vitro. 197 65

The effect of somatostatin-14 (SS-14) on gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission in the dorsolateral septal nucleus (DLSN) was investigated using a submerged slice preparation and intracellular recording techniques. Somatostatin-14 applied by superfusion or by pressure ejection from micropipettes predominantly inhibited the intracellularly recorded fast inhibitory postsynaptic potential (fIPSP) and late hyperpolarizing potential (LHP) elicited by focal electrical stimulation of the DLSN. The decreases in LHP and fIPSP amplitude occurred at low concentrations of peptide, in the absence of appreciable changes in the passive-membrane properties of postsynaptic neurons, and outlasted the membrane hyperpolarizing effect produced by SS-14 at higher concentrations. The ability of SS-14 to modulate postsynaptic GABA receptor responses underlying the fIPSP and LHP were investigated by applying baclofen, a selective GABAB receptor agonist, and isoguvacine, a selective GABAA receptor agonist, by pressure ejection. Hyperpolarizing responses to GABAA and GABAB receptor stimulation were significantly decreased during superfusion of SS-14. Tetrodotoxin applied by superfusion blocked electrically evoked synaptic potentials but not the depressant effect of SS-14 on baclofen- or isoguvacine-induced hyperpolarization. Facilitation of the fIPSP or LHP by SS-14 also occurred but less frequently and consistently than the depressant action. Excitatory postsynaptic potentials and membrane response to NMDA or quisqualate appeared unaltered by bath-applied SS-14. These findings suggest a novel postsynaptic action of SS-14 leading to depression of synaptic responses mediated by GABAA and GABAB receptors. Synaptically released SS-14 in the DLSN may participate in modulation of feedforward and/or feedback inhibitory mechanisms coordinating DLSN function in the septo-hippocampal system.
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PMID:Somatostatin depresses GABA receptor-mediated inhibition in the rat dorsolateral septal nucleus. 197 66

The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release.
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PMID:Role of gastrin in bombesin-stimulated somatostatin release. 197 61

1. The mechanical responses to some autonomic drugs and neuropeptides of longitudinal muscle (LM) and circular muscle (CM) strips isolated from the carp intestinal bulb were investigated in vitro. 2. Acetylcholine and carbamylcholine caused concentration-dependent transient contraction of both LM and CM strips. Tetrodotoxin had no effect, but atropine selectively decreased the contractile responses to acetylcholine and carbamylcholine. 3. Excitatory alpha-2 and inhibitory beta adrenoceptors were present in both LM and CM strips. 4. 5-Hydroxytryptamine (5-HT) caused concentration-dependent contraction of both LM and CM strips. Tetrodotoxin, atropine and methysergide decreased the contractile responses to 5-HT. 5. Some neuropeptides (angiotensin I, angiotensin II, bombesin, bradykinin, neurotensin, somatostatin and vasoactive intestinal polypeptide) did not cause any mechanical response (contraction or relaxation) in either smooth muscle strip. 6. Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) caused contraction of both LM and CM strips. However, the time course of the contraction in LM was different from that in CM. The order of potency was NKA greater than SP greater than NKB in LM strips and NKA greater than SP much greater than NKB in CM strips. In LM strips, the contractile responses to tachykinins were unaffected by spantide and methysergide, but partly decreased by tetrodotoxin and atropine. On the other hand, the contractile responses of CM strips were unaffected by tetrodotoxin, atropine, methysergide and spantide. 7. Dynorphin (1-13) (DYN), leucine-enkephalin (L-Enk) and methionine-enkephalin (M-Enk) caused concentration-dependent contraction of both LM and CM strips. The order of potency was DYN greater than M-Enk greater than L-Enk. Naloxone selectively decreased the responses to opiate peptides. 8. The present results indicate that acetylcholine, carbamylcholine, catecholamines, 5-HT, tachykinins (SP, NKA and NKB) and opiate peptides (DYN, L-Enk and M-Enk) affect the mechanical activity of LM and CM strips isolated from the carp intestinal bulb through their specific receptors.
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PMID:Effects of some autonomic drugs and neuropeptides on the mechanical activity of longitudinal and circular muscle strips isolated from the carp intestinal bulb (Cyprinus carpio). 198 39

Rat and human alpha- and beta-calcitonin gene-related peptide (CGRP), in the concentration range 1-100 nM, produced sustained relaxations of longitudinal muscle from the rat fundus and guinea pig gastric corpus. The peptides were equipotent and equally effective. Tetrodotoxin, adrenoceptor and purine receptor antagonists, somatostatin, apamin and Tyr-rat alpha-CGRP-(28-37) peptide did not modify the action of the CGRP peptides. The CGRP-induced responses were inhibited by verapamil and potentiated by Bay K-8644. Incubation of the tissues with indomethacin markedly reduced the magnitude of the CGRP- and adrenaline-induced relaxations, but their responsiveness was restored by addition of prostaglandins E1, E2 and F2 alpha in concentrations that alone did not affect the motility of the indomethacin-treated strips. It is suggested that an inhibitory receptor for CGRP on gastric smooth muscle cells is linked to calcium channels and may be activated or sensitized by endogenous prostaglandins.
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PMID:Calcitonin gene-related peptides relax guinea pig and rat gastric smooth muscle. 247 Jun

1. The stimulatory action of propionate on colonic electrolyte transport and involvement of the enteric reflex in this was studied in vitro using an Ussing chamber in the rat. The short-circuit current (Isc) and bidirectional fluxes of Na+ and Cl- were measured. Mucosa-submucosa preparations, containing the submucosal nerve, from the distal colon were used in most cases. 2. Mucosal application of propionate caused transient increases in the transmural potential difference, with the mucosal side negative, Isc and conductance. Serosal application of the acid had no effect. 3. Adaptation of the Isc response occurred when the acid was applied to the bathing solution cumulatively without washing out the first dose. If tissues were washed and held more than 20 min before the next application, the response was almost completely restored. 4. The increase in Isc in response to propionate was concentration dependent, with a 50% effective concentration of approximately 7 x 10(-5) M. 5. Two other short-chain fatty acids (SCFAs), n-butyrate and n-valerate, but not acetate, increased Isc when added to the mucosal bathing solution. 6. Bumetanide (3 x 10(-5) M) and the serosal chloride-free condition, but not amiloride (10(-4) M), inhibited the responses of Isc to propionate. Propionate-stimulated Cl- secretion resulted mainly from an increase in unidirectional serosal-to-mucosal Cl- movement. Propionate did not affect the Na+ flux. 7. Tetrodotoxin (10(-7) M), somatostatin (10(-7) M) and hexamethonium (10(-4) M) inhibited the propionate-evoked increase in Isc by 40, 70 and 30%, respectively. 8. Atropine (10(-5) M) also inhibited the Isc-increase response to propionate more than 90%. 9. Pre-treatment (2 min) of the mucosal surface with procaine (5 x 10(-4) M) inhibited the propionate-evoked increase in Isc by 90%. 10. The results suggest that luminal propionate transiently stimulated the colonic chloride secretory response that is not due to direct action on colonocytes, but due in large part to release of acetylcholine at neuro-colonocyte junctions, probably via an enteric reflex involving a mucosal sensory mechanism, cholinergic motor nerves and submucosal ganglia.
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PMID:Luminal propionate-induced secretory response in the rat distal colon in vitro. 247 96

Gallbladder mucosal net fluid transport and motility were measured in vivo by a continuous perfusion technique in the anaesthetized cat. Prostaglandin E2, administered to the perfused gallbladder lumen, caused a contraction decreasing gallbladder volume capacity, and induced a secretory response by the mucosa. These effects by prostaglandin E2 were abolished by the nerve-blocking agent tetrodotoxin (administered close intraarterially) and somatostatin (administered intravenously), but not by intravenous hexamethonium. Atropine (administered intravenously) reduced the order of magnitude of the gallbladder contraction in response to prostaglandin E2 but did not affect the secretory response by the mucosa. Neither of these drugs significantly affected gallbladder volume capacity or mucosal fluid transport during basal conditions. Tetrodotoxin did not abolish the gallbladder responses to intravenous cholecystokinin or vasoactive intestinal peptide, peptides known to act directly upon smooth muscle and epithelial cell receptors, respectively. It is suggested that prostaglandin E2 affects gallbladder function in vivo mainly by activation of postganglionic non-cholinergic intramural nerve cells.
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PMID:Intraluminal prostaglandin E2 affects gallbladder function by activation of intramural nerves in the anaesthetized cat. 290 7

Neuropeptide Y (NPY) is present in fibers extending from the submucous plexus to the epithelium of the small intestine where the liberation of NPY might affect ion transport. We sought the effects of NPY on rabbit ileal mucosa stripped of muscularis propria and mounted in a flux chamber. NPY reduced the transmural electrical potential difference and short circuit current (Isc) and increased total ionic conductance. Threshold and maximal effects were evoked at concentrations of 1 nM and 1 microM, respectively. NPY increased chloride absorption, JCl(net), by increasing the flux of Cl from mucosa to serosa, JCl(ms), and by decreasing JCl(sm). JNa(net) actually diminished because JNa(sm) rose more than JNa(ms). In the presence of NPY theophylline 5 mM caused Cl secretion, increased potential difference and Isc and reduced total ionic conductance, indicating that the tissue could respond to a secretagogue. Tetrodotoxin 0.1 microM did not diminish the Isc reduction caused by NPY, and desensitization did not alter the response of the tissue to electrical field stimulation. Like somatostatin and norepinephrine, which are also present in the submucous plexus, NPY increases Cl absorption, but unlike them, it reduces rather than augments Na absorption. The lack of effect of tetrodotoxin on the Isc response to NPY implies that NPY does not act by liberating a second neurotransmitter; the lack of effect of NPY desensitization indicates that the liberation of NPY plays no significant role in the response of the tissue to electrical field stimulation.
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PMID:Effect of neuropeptide Y on ion transport by the rabbit ileum. 375 70

Primary cultures of dispersed hypothalamic cells were prepared from embryonic rats to study the release of immunoreactive somatostatin. The immunoreactive somatostatin content of these cultures increased during the first 2 weeks after plating and was readily measurable for several weeks thereafter; this material was characterized by gel permeation and reverse-phase chromatography. Depolarization of the cells with 60 mM K+ or with veratridine resulted in a calcium-dependent release of immunoreactive somatostatin which cochromatographed with synthetic somatostatin on reverse-phase chromatography. Tetrodotoxin blocked the veratridine-evoked release. However, even in the absence of exogenous stimuli, immunoreactive somatostatin was released by the cells into the medium. More than 70% of this tonic release was found to be calcium dependent and to be inhibited by tetrodotoxin, indicating that spontaneous electrical activity in the cultures leads to a release of immunoreactive somatostatin. gamma-Aminobutyric acid inhibited the tonic release of immunoreactive somatostatin and this was reversed by bicuculline. These findings support the hypothesis that gamma-aminobutyric acid inhibits somatostatin release in vivo.
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PMID:Release of immunoreactive somatostatin from hypothalamic cells in culture: inhibition by gamma-aminobutyric acid. 610 13


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