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)

Somatostatin (SS) in 10(-9)-10(-7) M concentrations stimulated the lysis and inhibited the incorporation of IgG2a-coated 51Cr-labeled sheep red blood cell (SRBC) by rat peritoneal macrophages (PM). The intracellular killing capacity of PM remained unchanged. The enhancement of Fc receptor (R) activity and generation of active oxygen species were found to be responsible for the antibody-dependent cellular cytotoxicity (ADCC)-stimulating effect of SS. It was demonstrated that the stimulation of ADCC was abolished by the calmodulin inhibitor trifluoperazine (TFP), whereas it proved to be independent of the Ca2+ uptake. In addition, SS in the ADCC-stimulating concentrations diminished the intracellular cAMP generation and progressively increased the cGMP level. In higher (10(-6)-10(-7) M) concentrations, SS had a controversial effect on PM: it inhibited ADCC through the activation of both the adenylate cyclase and Ca2+ influx.
 ...
PMID:The mechanism of antibody-dependent cellular cytotoxicity stimulation by somatostatin in rat peritoneal macrophages. 285 14

Somatostatin has been found to inhibit secretion vesicle fusion with the iodinated (125-I) inside-out plasma membrane vesicles (both were isolated from the anterior pituitaries). This effect of somatostatin was specific and dose-dependent (half-maximal effect at 10(-9) M). Calmodulin (10 microM), but not cyclic AMP, enhanced the fusion process between the two organelles and somatostatin inhibited calmodulin-stimulated fusion. These observations suggest that one facet of somatostatin action on hormone secretion may be its inhibition of secretion vesicle fusion with the plasma membrane.
 ...
PMID:Somatostatin inhibits fusion of pituitary secretion vesicles with the plasma membranes. 287 5

Experiments were performed in vitro to examine the possible role of calcium and calmodulin in GRF-induced somatostatin (SRIF) release from the median eminence. Adult male rats were used as tissue donors. The median eminences were first prestimulated in 0.4 ml Krebs Ringer bicarbonate glucose buffer (pH 7.4) containing bacitracin at 37C in an atmosphere of 95% O2, 5% CO2 with constant shaking for 30 min. When calcium was omitted, this medium was used during the prestimulation and stimulation periods. After prestimulation, the medium was discarded and replaced by medium containing the different substances to be tested (GRF, EGTA, calcium channel blockers, and calmodulin inhibitors). The stimulation of SRIF release induced by 10(-10) M GRF was not inhibited by omission of extracellular calcium or when the remaining CA+2 was chelated with 10(-4) M EGTA. The calcium channel blockers, nifendipine and verapamil (10(-6) M), failed to alter the increase of SRIF release induced by rGRF. Three calmodulin inhibitors were employed to examine the possible influence of calmodulin on GRF-induced SRIF release. Trifluoperazine (10(-6) M), triflupromazine (10(-6) M) and penfluridol (10(-7) M) had an inhibitory effect on the stimulation of SRIF release induced by GRF and failed to alter resting release. Thus, GRF can evoke SRIF release independently of extraterminal Ca+2 concentration and Ca+2 influx into the nerve terminals, but the releasing process involves translocation of Ca+2 from intracellular stores. The inhibitory effect of the calmodulin inhibitors on GRF-induced SRIF release, suggests that the translocated Ca+2 must bind to calmodulin in order to release SRIF.
 ...
PMID:Calmodulin dependence of somatostatin release stimulated by growth hormone-releasing factor. 289 60

The chain of events leading to the manifestation of the biological action of somatostatin are described. Internalization is mediated by cytoskeletal proteins in the presence of calmodulin. Transduction of the somatostatin message at the membrane level takes place through inhibition of cyclic AMP accumulation and blockade of cytosol calcium increases. The influence of central and peripheral factors upon these processes is discussed and the importance of the Ni/Ns components is stressed. Thus, somatostatin also suppresses phosphoinositide turnover and stimulates soluble phosphodiesterase, thus reinforcing its negative effect on cyclase generation.
 ...
PMID:Mechanism of action of somatostatin. 290 Jan 97

The role of calcium (Ca2+) in bombesin (BBS)-stimulated release of gastrin and somatostatin-like immunoreactivity (SLI) was examined in isolated perfused rat stomachs obtained from male rats fasted overnight. The stomachs were perfused via the celiac artery. BBS (1 nM) was perfused alone for 10 min or in combination with various Ca2+ antagonists, including 1) different doses of divalent cationic Ca2+ chelator (EGTA), 2) Ca2+ channel blockers (nifedipine, verapamil), and 3) calmodulin (Ca2+ binding protein) antagonist [trifluoperazine (TFP)]. The effluent was collected for measurement of gastrin and SLI. EGTA at doses of 2 or 5 mM blocked the BBS-mediated release of both gastrin and SLI. After removal of a low dose of EGTA from the perfusate, the release of both gastrin and SLI rebounded. On removal of a high dose of EGTA, however, SLI release remained depressed, but gastrin rebounded even more significantly. In the absence of BBS, the rebound of gastrin release was less dramatic, indicating that reexposure to Ca2+ partially contributed to the rebound phenomenon. Nifedipine (0.1-10 microM) markedly decreased BBS-stimulated release of gastrin and SLI in a dose-dependent fashion; the inhibitory effect of nifedipine on SLI release was significantly stronger than on gastrin release. Verapamil (10 microM) depressed BBS-induced SLI release but not gastrin release. TFP (50 or 100 microM) also resulted in inhibition of bombesin-elicited release of gastrin and SLI in a dose-related manner.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of Ca2+ in bombesin-stimulated release of gastrin and somatostatin from isolated perfused rat stomach. 290 76

Hormonal activation and inhibition of the GH4Cl1 cell adenylate cyclase complex is delineated. In the presence of the guanyl nucleotide GTP, enzyme activity was enhanced twofold by thyroliberin, sixfold by vasoactive intestinal peptide (VIP), twofold by prostaglandin E2 and twofold by isoproterenol. The diterpene, forskolin, increased, the activity 14-fold. In the presence of high GTP (400 microM) and NaCl (150 mM) concentrations, somatostatin inhibited (ED50 = 0.5 microM) the cyclase activity by 40%. In the presence of 10 microM somatostatin, the ED50 values (5 nM) for thyroliberin- and VIP-stimulated adenylate cyclase activities were shifted to 20 nM. Forskolin-elicited activation was, however, not affected by somatostatin. Cholera-toxin and pertussis-toxin pretreatment of the enzyme brought about some 20-fold and twofold activation, respectively. Inhibition by somatostatin was abolished upon pre-exposure to pertussis toxin. Mild alkylation by N-ethylmaleimide increased basal and hormone-activated adenylate cyclase while somatostatin again failed to express its inhibitory potential. Further alkylation caused a gradual decline and convergence of hormone-modulated cyclase activities towards zero. The N-ethylmaleimide-induced attenuation of thyroliberin-elicited activity was paralleled by a decrease in [3H]thyroliberin binding. Trifluoperazine and an anti-calmodulin serum reduced basal and net thyroliberin-, VIP- and forskolin-enhanced cyclase activities by some 30%, 100%, 70% and 80%, respectively. The Vmax of basal and thyroliberin-stimulated adenylate cyclase was diminished by 65%, leaving the apparent Km values (7.2 mM and 2.6 mM, respectively) for Mg2+ unaltered. Finally, the phorbol ester 12-O-tetra-decanoyl-phorbol 13-acetate (TPA) doubled the activity. This effect was counteracted by the protein kinase C inhibitor, polymyxin B, while thyroliberin-enhanced adenylate cyclase remained unaffected. In summary, we have described an adenylate cyclase with stimulatory (Rs) and inhibitory (Ri) receptors coupled to a calmodulin-sensitive holoenzyme through the Gs and Gi type of GTP-binding proteins. The ratio of the Gs to Gi is high. It appears that the GH4C1 cell adenylate cyclase is also activated by protein kinase C by interference with Gi. Apparently, thyroliberin activates the cyclase both directly through Gs and indirectly via protein kinase C stimulation.
 ...
PMID:Hormone-sensitive adenylate cyclase of prolactin-producing rat pituitary adenoma (GH4C1) cells: molecular organization. 290 68

Somatostatin administration to female rats increased the activity of calmodulin-dependent soluble phosphodiesterase, both in pituitary and brain. This effect was also seen in homogenates of GH4C1 cells pretreated with the hormone. When assayed in the presence of EGTA no differences in rat brain and pituitary phosphodiesterase were observed between controls and somatostatin-treated, but when assayed in the presence of calcium or calcium plus calmodulin a clear increase in the activity of the enzyme was detected. In GH4C1 homogenates prepared from somatostatin-pretreated cells there was an increase in phosphodiesterase activity assayed in the presence of EGTA vs non-treated controls, which was more clear when assayed in the presence of calcium or calcium plus calmodulin. These observations suggest that somatostatin effects derive, at least in part, from increased cyclic nucleotide degradation.
 ...
PMID:Somatostatin stimulates phosphodiesterase in rat anterior pituitary and brain, and GH4C1 cells. 290 90

Bordetella pertussis synthesizes a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changed the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. We conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is this response that explains the subsequent acceleration of hormone release.
 ...
PMID:Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture. 301 20

In this study a synthetic analog of the calmodulin-binding domain of myosin light chain kinase, a 17-amino-acid peptide (M5) was used to examine the possible role of calmodulin in melanotropin receptor function. Binding of beta-melanocyte-stimulating hormone to its membrane receptor and subsequent stimulation of adenylate cyclase (AC) were found to be specifically inhibited by M5 in a dose-dependent and noncompetitive manner, both in intact M2R melanoma cells and in a plasma membrane preparation derived thereof. Half-maximal inhibition of both hormone binding and melanotropin-sensitive AC activity was shown to occur at approximately 1 microM M5. In contrast, stimulation of AC by prostaglandin E1, guanosine 5'-O-(3-thio)triphosphate, forskolin, and unstimulated enzyme activity were unaffected by the presence of M5, under the same assay conditions. Furthermore, addition of a molar excess of calmodulin to the AC assay completely abolished the inhibitory effects of the peptide on melanotropin-stimulated AC activity. Other peptides of similar size, which bind to calmodulin with low affinity (e.g. glucagon, somatostatin, and vasoactive intestinal peptide), were shown to be totally ineffective in inhibiting melanotropin-sensitive AC. These findings, along with those shown previously for other antagonists of calmodulin, suggest a role for an M5-binding protein, as of yet unidentified, involved in the regulation of the melanotropin receptor function.
 ...
PMID:A synthetic analog of the calmodulin-binding domain of myosin light chain kinase inhibits melanotropin receptor function and activation of adenylate cyclase. 336 68

Recent advances in understanding of intestinal fluid and electrolyte absorption have paved the way for the development of antidiarrheal agents specific for various points in the secretory and absorptive process. Examples of potential antidiarrheal agents include clonidine and lidamidine in diabetic diarrhea, somatostatin in hormonally mediated diarrhea, and prostaglandin synthetase inhibitors in inflammatory diarrhea. Physiological principles of electrolyte transport that underlie these new developments include the capability in both the small and large intestine of the epithelium in absorbing and secreting water and electrolytes; the responsibility of the villus epithelium for sodium chloride/water absorption and of the crypt epithelium for chloride/water secretion; the existence of a continuum between absorption and secretion determined by the sum of the absorptive and secretory drives on the enterocyte; the role of neuroendocrine transmitters, hormones, and inflammatory elements released systemically or locally as stimuli regulating these processes; the fact that most of these stimuli activate specific receptors on enterocytes; and the altering effect of these stimulus-receptor interactions on intercellular levels of cyclic nucleotides or calcium, in turn producing net secretion by diminishing absorption and/or stimulating secretion. Also under investigation as antidiarrheal agents are calcium and calmodulin antagonists, enkephalins, lithium, berberine, oral organic acids, and chloride channel blockers.
 ...
PMID:Antidiarrheal therapy. Prospects for new agents. 354 47


<< Previous 1 2 3 4 5 Next >>