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)

The effects of somatostatin-28, somatostatin-14, and a synthetic somatostatin octapeptide analogue, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (cyclo SS-8) were examined on contraction of dispersed gastric smooth muscle cells from guinea pigs. The somatostatins did not cause contraction of gastric smooth muscle cells, nor did they inhibit carbachol-stimulated contraction. However, they reversed vasoactive intestinal peptide (VIP)-induced inhibition (relaxation) of carbachol-stimulated contraction. Somatostatin-28 had a half-maximal effect (EC50) at 1.6 +/- 0.8 nM, cyclo SS-8 at 0.6 +/- 0.3 nM, but somatostatin-14 had no effect even when used in concentrations as high as 1 microM. Incubation of muscle cells with peptidase inhibitors phosphoramidon (1 microM) plus amastatin (10 microM) had no effect on the EC50 of somatostatin-28 or cyclo SS-8 but increased the potency of somatostatin-14 greater than 1,000-fold. When peptides were incubated with muscle cells and the products applied to high-performance liquid chromatography, cyclo SS-8 was not degraded, but somatostatin-14 was rapidly degraded when present alone, and the addition of peptidase inhibitors partially inhibited the degradation. Cyclo SS-8 had its maximal effect at 0.5-1 min and inhibited relaxation induced by VIP, isoproterenol, glucagon, or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Cyclo SS-8 partially inhibited the increase in VIP-stimulated cAMP. Preincubation with pertussis toxin blocked the inhibitory action of cyclo SS-8 on VIP or DBcAMP-induced relaxation. These results indicate that gastric smooth muscle cells rapidly degrade somatostatin-14 and suggest that muscle cell peptidases could have a major effect on the actions of somatostatin-14.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Actions of somatostatins on gastric smooth muscle cells. 134 75

We have recently shown that in rat parietal cells the glucagon-like peptide 1 (GLP-1) variants 7-36 amide, 1-37, and 1-36 amide stimulate H+ production as indirectly measured by [14C]aminopyrine (AP) accumulation. This response to the GLP-1 peptides was intracellularly mediated by activation of adenylate cyclase and by adenosine 3',5'-cyclic monophosphate (cAMP) as second messenger. In the present study, we compared prostaglandin (PG)E2, somatostatin, and the protein kinase A antagonist Rp-adenosine-3',5'-monophosphorothioate (Rp-cAMPS) with respect to their inhibitory effects on parietal cell function induced by GLP-1 or histamine. PGE2 and somatostatin noncompetitively inhibited AP accumulation and cAMP production in response to the GLP-1 variants and histamine (IC50): [mean inhibitory concn 5 x 10(-9) M PGE2; 3 x 10(-7) somatostatin]; at their maximal concentrations PGE2 (10(-7) M) and somatostatin (10(-6) M) caused 85 and 65% inhibition, respectively. Treatment with pertussis toxin (PT; 250 ng/ml; 4 h) reversed the inhibitory effect of PGE2 and somatostatin on AP accumulation and cAMP production. At 2 x 10(-3) M (IC50: 3 x 10(-4) M) Rp-cAMPS completely inhibited AP accumulation induced by the GLP-1 variants or histamine; this effect was insensitive to PT. Specificity of Rp-cAMPs as protein kinase A inhibitor is suggested by inhibition of AP accumulation in response to Sp-cAMPS and N6,O2-dibutyryl adenosine 3',5'-cyclic phosphate sodium, and forskolin, activators of protein kinase A and adenylate cyclase, respectively. We conclude that the parietal cell responses to GLP-1 and histamine are inhibited by identical mechanisms. Effects of PGE2 and somatostatin are mediated by the PT-sensitive subunit of adenylate cyclase Gi, whereas Rp-cAMPS interferes with cAMP-dependent mechanisms that are insensitive to PT.
 ...
PMID:Pertussis toxin-sensitive and pertussis toxin-insensitive inhibition of parietal cell response to GLP-1 and histamine. 134 5

Actions of human calcitonin-gene related peptide (hCGRP) on acetylcholine (ACh) discharge and gastrin and somatostatin release from rat antral mucosal-submucosal fragments were examined in both dynamic perifusion experiments and short-term static incubation studies. The principal findings of the dynamic perifusion experiments were that hCGRP exerted a dual or biphasic effect on ACh discharge and gastrin release. Initial exposure of antral tissues to hCGRP (1 x 10(-8) M) resulted in stimulation of both ACh and gastrin release that was of brief duration. Continued hCGRP perifusion caused subsequent inhibition of ACh and gastrin release that was substantially greater in duration and magnitude than the initial stimulatory responses. Static incubation studies indicated that hCGRP (10(-10) to 10(-7) M) stimulated somatostatin and inhibited gastrin release in a dose-dependent manner. Inhibition of gastrin and ACh release by hCGRP appeared to be an indirect effect that was mediated by somatostatin as suggested by studies with pertussis toxin (200 ng/ml). Furthermore, studies with atropine (1 x 10(-6) M) and tetrodotoxin (1 x 10(-6) M) indicated that CGRP-induced stimulation of somatostatin release and inhibition of ACh discharge occurred independent of muscarinic receptor activation and nerve excitation. In conclusion, results of these studies indicate that CGRP is capable of exerting both stimulatory and inhibitory effects on ACh release from mucosal-submucosal neurons and gastrin release from antral mucosal G cells in in vitro studies. These data suggest that the inhibitory effects of CGRP on cholinergic discharge and gastrin release are due to the paracrine effects of somatostatin released from antral D cells by direct action of CGRP.
 ...
PMID:Calcitonin gene-related peptide: mechanisms of modulation of antral endocrine cells and cholinergic neurons. 134 8

Leu-enkephalin (Leu-Enk), norepinephrine (NE), somatostatin (SS), and bradykinin (BK) decrease the voltage-dependent calcium current in NG108-15 cells. Here we have investigated whether distinct G proteins, or a G protein common to all of the pathways, mediates this inhibition. We found that pertussis toxin (PTX) reduced all of these transmitter actions, except that of BK. To examine which of the PTX-sensitive pathways is transduced by GoA, we constructed an NG108-15 cell line that stably expresses a mutant, PTX-resistant alpha subunit of GoA. After treatment with PTX, the mutant GoA alpha rescued the Leu-Enk and NE pathways but not the SS pathway. At least three different G proteins can transduce receptor-mediated inhibition of calcium currents in nerve cells. The effects of these G proteins appear to converge on the omega-conotoxin GVIA-sensitive calcium current.
 ...
PMID:Inhibition of the omega-conotoxin-sensitive calcium current by distinct G proteins. 134 51

Bradykinin (BK) induced a transient and pertussis toxin (PT)-insensitive increase in cytosolic Ca2+ ([Ca2+]i) in NG 108-15 neuroblastoma x glioma hybrid cells, whereas leucine-enkephalin (EK), somatostatin, norepinephrine or carbachol showed a weak but PT-sensitive action. When any one of the latter agonists was applied to the cells treated with low doses of BK, however, the level of [Ca2+]i rise caused by the agonist was remarkably increased in a PT-sensitive manner. The decreasing of extracellular Ca2+ only slightly influenced the actions of these agonists. Thus, synergism between a BK receptor and PT-sensitive G-protein-coupled receptors results in marked intracellular Ca2+ mobilization by the latter agonists.
 ...
PMID:Synergism in cytosolic Ca2+ mobilization between bradykinin and agonists for pertussis toxin-sensitive G-protein-coupled receptors in NG 108-15 cells. 134 83

Somatostatin has recently been applied therapeutically for hypercalcitonemia in patients with calcitonin-producing tumours. Using calcitonin-secreting cells (C-cells) of the medullary thyroid carcinoma cell line rMTC 44-2, we investigated the inhibitory action of somatostatin on calcitonin release, cytosolic Ca2+ and Ca2+ channel currents. The Ca(2+)-induced rises of the cytosolic Ca2+ and calcitonin secretion were greatly inhibited by somatostatin or its stable analogue octreotide. The effects of somatostatin were pertussis toxin-sensitive. Under voltage clamp conditions, C-cells exhibited slowly inactivating Ca2+ channel currents. Bath application of 100 nM somatostatin reversibly reduced the Ca2+ channel current by about 30%. The Ca2+ channel current and its inhibition by somatostatin were not affected by intracellularly applied cyclic AMP. Moreover, pretreating the cells with pertussis toxin had no effect on the control Ca2+ channel currents but greatly abolished its inhibition by somatostatin. The data show that somatostatin suppresses the Ca(2+)-stimulated calcitonin secretion by inhibiting voltage-dependent Ca2+ channel currents and by lowering cytosolic Ca2+. These actions of somatostatin involve pertussis toxin-sensitive G-proteins and occur independently of changes in the cyclic AMP concentration.
 ...
PMID:Inhibition of Ca(2+)-induced calcitonin secretion by somatostatin: roles of voltage dependent Ca2+ channels and G-proteins. 134 29

To clarify the possible role of a guanine nucleotide-binding protein (G-protein) in the signal transducing system activated by carbachol, actions of carbachol on human pancreastatin producing cell line (QGP-1N) were compared with those of fluoride, a well-known activator of stimulatory (Gs) or inhibitory (Gi) G protein. 10(-5) M of carbachol as well as 20 mM of NaF stimulated secretion of pancreastatin and somatostatin and intracellular Ca2+ mobilization. These secretion and Ca2+ mobilization were not modified by pertussis toxin, an inhibitor of Gi protein. These results suggest that pancreastatin and somatostatin secretions from QGP-1N are regulated by acetylcholine through a muscarinic receptor coupled to the activation of polyphosphoinositide breakdown by a G protein, which appears to be fluoride sensitive but is other than a Gi-like protein.
 ...
PMID:Pertussis toxin non-sensitive G protein mediates cholinergic stimulation for secretion of pancreastatin and somatostatin from QGP-1N cells. 135 Jan 5

We evaluated the transmembrane signaling mechanism that may underlie the facilitatory action of somatostatin (SOM) on baroreceptor reflex (BRR), using adult, male, Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Intracerebroventricular (i.c.v.) application of SOM (2 nmol) promoted a significant elevation in BRR response, induced by phenylephrine (5 micrograms/kg, i.v.). This potentiatory action of the tetradecapeptide was significantly reversed after pretreating animals with bilateral microinjection of pertussis toxin (25 ng) or N-ethylmaleimide (2 nmol) into the nucleus tractus solitarius (NTS), the terminal site for baroreceptor afferents. These results suggest that a pertussis toxin-sensitive GTP-binding regulatory protein, possibly Gi, may be involved in the modulation of the BRR by SOM at the NTS.
 ...
PMID:Reversal by pertussis toxin and N-ethylmaleimide of the facilitation of baroreceptor reflex response by somatostatin in the rat. 135 Mar 36

These studies were performed to determine the intracellular pathways involved in regulating gastrin gene expression. The inclusion of 10(-4) M forskolin or 10(-4) M dibutyryl cyclic AMP (DBcAMP) in incubation medium containing dog antral mucosa resulted in 249% and 323% increases, respectively, in gastrin mRNA levels. The stimulatory effects of forskolin and DBcAMP were both inhibited significantly by 10(-6) M somatostatin. Preincubation of antral mucosa with pertussis toxin nearly abolished the inhibitory effects of somatostatin on gastrin mRNA stimulated by forskolin, but had no effect following DBcAMP. To examine whether calcium-dependent pathways might be involved in regulating gastrin gene expression, antral mucosa was incubated with increasing concentrations of calcium or the ionophore ionomycin. Both agents produced only modest increases in gastrin mRNA, which were abolished by the addition of somatostatin to the incubation medium. These studies indicate that somatostatin appears to inhibit gastrin gene expression through mechanisms involving both pertussis toxin-sensitive and -insensitive pathways.
 ...
PMID:Somatostatin inhibition of gastrin gene expression: involvement of pertussis toxin-sensitive and -insensitive pathways. 135 Mar 57

The growth-inhibiting peptide hormone somatostatin stimulates phosphotyrosine phosphatase activity in the human pancreatic cell line MIA PaCa-2. This hormonal activation was mediated by a pertussis toxin-sensitive guanosine 5'-triphosphate-binding protein (G protein) in the membranes of these cells. Activation of this G protein by somatostatin stimulated the dephosphorylation of exogenous epidermal growth factor receptor prepared from A-431 cells in vitro. This pathway may mediate the antineoplastic action of somatostatin in these cells and in human tumors and could represent a general mechanism of G protein coupling that is utilized by normal cells in the hormonal control of cell growth.
 ...
PMID:G protein activation of a hormone-stimulated phosphatase in human tumor cells. 135 Mar 82


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