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)

1. The effects of somatostatin and somatostatin analogues on a Ca2+ current from acutely isolated and short-term (24-48 h) cultured adult rat superior cervical ganglion (SCG) neurones were studied using the whole-cell variant of the patch-clamp technique. 2. [D-Trp8]Somatostatin (SOM) produced a rapid, reversible and concentration-dependent reduction of the Ca2+ current. Ca2+ current amplitude was reduced over the voltage range -15 to +40 mV with the greatest reduction occurring where the amplitude was maximal (ca +10 mV). In the presence of SOM, the Ca2+ current rising phase was slower and biphasic at potentials between 0 and +40 mV. 3. Application of 0.1 microM-SOM for greater than 10 s resulted in a desensitization of the response. During a 4 min application of 0.1 microM-SOM, Ca2+ current amplitude returned to about 90% of control. A second application of 0.1 microM-SOM produced less block than the initial application. 4. Concentration-response curves for SOM, somatostatin-14 (SOM-14) and somatostatin-28 (SOM-28) were fitted to a single-site binding isotherm. The concentrations producing half-maximal block and the maximal attainable blocks of the Ca2+ current for SOM, SOM-14 and SOM-28 were 3.3, 5.4 and 35 nM, respectively and 55, 51 and 54%, respectively. SOM-14 and SOM-28 slowed the Ca2+ current rising phase in a manner similar to that of SOM. Somatostatin-28 had no effect on the Ca2+ current at 1 microM. 5. The magnitude of the Ca2+ current block produced by 0.1 microM-SOM was not significantly altered in the presence of 1 microM-idazoxan, atropine, naloxone or the somatostatin antagonist aminoheptanoyl-Phe-D-Trp-Lys-O-benzyl-Thr. 6. Internal dialysis with solutions containing 500 microM-guanylyl-imidodiphosphate (Gpp(NH)p) or guanosine-5'-O-(3-thiotriphosphate)(GTP-gamma-S) decreased the Ca2+ current amplitude by 36 and 41%, respectively, and induced a biphasic rising phase in the Ca2+ current. Under these conditions, application of 0.1 microM-SOM produced significantly less block of Ca2+ current amplitude (7.1 and 14.7%, respectively) when compared with controls. 7. Internal dialysis with solutions containing 500 microM-guanosine-5'-O-(2-thiodiphosphate)(GDP-beta-S) had no significant effect on either the Ca2+ current amplitude or block produced by 0.1 microM-SOM. 8. Internal dialysis with solutions containing 500 microM-cyclic adenosine 3',5'-monophosphate (cyclic AMP) and 3-isobutyl-1-methylxanthine had no significant effect on either the Ca2+ current block produced by 0.1 microM-SOM or the Ca2+ current amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Somatostatin blocks a calcium current in rat sympathetic ganglion neurones. 247 36

This paper was addressed to know whether early events in mitogenesis (activation of the Na+/H+, activation of ornithine decarboxylase and formation of cyclic AMP) are involved in pancreatic cell proliferation and mediate secretory process. The AR4-2J cell line was used. Analogues of amiloride inhibited cell proliferation but had no effect on amylase release. Activation of ornithine decarboxylase was triggered via a CCK B receptor type not involved in pancreatic secretion. Inhibition of cyclic AMP was not involved in inhibition of cell proliferation caused by somatostatin. Specific effectors might be related either to the secretory or to the trophic pathway. Another possibility is that multiple receptor sub-classes are linked to specific pathways.
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PMID:Interrelation of secretory and trophic responses in the exocrine pancreas. 248 97

Tetradecanoyl phorbol acetate (TPA) stimulates growth hormone (GH) and prolactin secretion from ovine anterior pituitary cells. Pretreatment of the cells with TPA abolishes this effect, presumably due to down-regulation of protein kinase C. Such pretreatment did not alter effects of thyrotropin-releasing hormone or dopamine on prolactin secretion, suggesting no involvement of protein kinase C. Pretreatment with TPA attenuated actions of GH-releasing hormone on GH release (but not actions on cyclic AMP levels), possibly due to depletion of cellular stores of GH. Such pretreatment also attenuated inhibition of GH release by somatostatin, possibly due to phosphorylation of receptors or associated proteins by protein kinase C.
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PMID:Effects of pretreatment with tetradecanoyl phorbol acetate on regulation of growth hormone and prolactin secretion from ovine anterior pituitary cells. 254 31

Acute and chronic hypopituitarism is associated with severe envenoming by the Burmese Russell's viper. We have demonstrated that in vitro, Burmese Russell's viper venom (0.1-10 micrograms/ml) causes a dose-dependent release of GH, TSH and ACTH from dispersed rat anterior pituitary cells in culture. At 10 micrograms/ml, venom causes a significant increase in the release of GH (344%, P less than 0.001), TSH (168%, P less than 0.005) and ACTH (greater than 700%, P less than 0.001). We have also shown that the component (or components) responsible for this stimulatory effect is stable to heat (60 degrees C, 1 h) and mild trypsinization. Repeated addition of venom (1 microgram/ml) to pituitary cells in a perifusion column system demonstrated attenuation of GH release. This reduced response was not due to depletion of the GH pool since the pituitary cells were subsequently able to respond to both GH-releasing factor (GRF) stimulation and KCl depolarization. Somatostatin in a dose which abolished GRF-stimulated GH release failed to affect venom-stimulated GH release, implying that venom acts in a cyclic AMP-independent manner. We conclude that Burmese Russell's viper venom has direct effects on pituitary hormone release in vitro. Whether these effects contribute to its known actions in vivo on the function of the pituitary remains to be established.
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PMID:Burmese Russell's viper venom causes hormone release from rat pituitary cells in vitro. 254 60

Phenotypically distinct islet tumor cell lines may recapitulate certain of the developmental pathways of normal islet cell differentiation by expressing a combinatorial set of positively and negatively acting DNA-binding proteins to allow for the programmed expression of genes encoding polypeptide hormones. The structure of one of these DNA-binding proteins, a cyclic AMP-responsive protein (CREB) that binds specific DNA regulatory elements in the somatostatin gene, has been deduced from the sequence of a cloned cDNA. The CREB protein contains a DNA-binding domain separate from a cAMP-dependent protein kinase A activation domain. Further characterizations of the genes encoding the DNA-binding proteins should help to elucidate the cellular processes involved in islet cell differentiation and the genesis of tumors.
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PMID:Factors that determine cell-specific gene expression in pancreatic endocrine tumor cells. 255 19

Binding of [125I]monoiodoinsulin to human astrocytoma cells (U-373 MG) was time dependent, reaching equilibrium after 1 h at 22 degrees C with equilibrium binding corresponding to 2.2 fmol/mg protein: this represents approximately 2,000 occupied binding sites per cell. The t1/2 of 125I-insulin dissociation at 22 degrees C was 10 min; the dissociation rate constant of 1.1 X 10(-2) s-1 was unaffected by a high concentration of unlabeled insulin (16.7 microM). Porcine insulin competed for specific 125I-insulin binding in a dose-dependent manner and Scatchard analysis suggested multiple affinity binding sites (higher affinity Ka = 4.4 X 10(8) M-1 and lower affinity Ka = 7.4 X 10(6) M-1). Glucagon and somatostatin did not compete for specific insulin binding. Incubation of cells with insulin (0.5 microM) for 2 h at 37 degrees C increased [2-14C]uridine incorporation into nucleic acid by 62 +/- 2% (n = 3) above basal. Cyclic AMP, in the absence of insulin, also stimulated nucleoside incorporation into nucleic acid [65 +/- 1% (n = 3)] above basal. Preincubation with cyclic AMP followed by insulin had an additive effect on nucleoside incorporation [160 +/- 4% (n = 3) above basal]. Dipyridamole (50 microM), a nucleoside transport inhibitor, blocked both basal and stimulated uridine incorporation. These studies confirm that human astrocytoma cells possess specific insulin receptors with a demonstrable effect of ligand binding on uridine incorporation into nucleic acid.
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PMID:Insulin binding to human astrocytoma cells and its effect on uridine incorporation into nucleic acid. 256 7

Cachectin (tumor necrosis factor) is a powerful macrophage hormone released during infection, which circulates in blood to produce diverse effects in the organism. We examined the effect of cachectin on release of anterior pituitary hormones from either hemipituitaries or dispersed pituitary cells incubated in vitro. The action of cachectin on dispersed cells was demonstrable only after 2 hr of incubation. With this incubation time, the protein produced a dose-related stimulation of release of adrenocorticotropin (ACTH), growth hormone (GH), and thyrotropin (TSH), but not of prolactin (Prl), from both hemipituitaries and dispersed cells. The doses required for stimulation were low in the case of hemipituitaries, usually of the order of 10(-12) M, whereas they were higher by one or two orders of magnitude with the dispersed pituitary cells. This may be related either to loss of receptors for the protein during the dispersion procedure or to the fact that in the hemipituitary system cell interactions are facilitated because the cells are close to each other. In the dispersed cell system cachectin evoked a dose-related decrease in cyclic AMP content. Incubation with somatostatin lowered the cyclic AMP content of the cells and depressed GH output without altering output of TSH or Prl. When somatostatin and cachectin were incubated together with the cells, the suppression of cyclic AMP production was abolished; TSH and Prl release were stimulated, but the action of cachectin to stimulate GH release was blocked. The stimulation of Prl release by cachectin in the presence of somatostatin may be related to the elevation of cyclic AMP, a known stimulator of Prl release. The cyclooxygenase inhibitor indomethacin nearly completely blocked the stimulatory effect of cachectin on release of GH and TSH from dispersed pituitary cells but had only a slight and nonsignificant attenuating effect on its ACTH-releasing action. These results suggest that at least part of the stimulatory action of the peptide on pituitary hormone release is brought about by prostaglandins. The failure of indomethacin to block the release of ACTH induced by cachectin suggests that other mechanisms may be involved in the release of ACTH induced by this peptide. Since the concentrations of cachectin required to stimulate pituitary hormone release are similar to those that are encountered in plasma during infection, it is likely that this direct pituitary action has pathophysiological significance.
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PMID:Cachectin alters anterior pituitary hormone release by a direct action in vitro. 256 80

The Mongolian gerbil, with its spontaneous epileptiform seizures, was chosen as an experimental model of human epilepsy. Neurochemical parameters possibly related to the seizure process were studied. In the immediate seizure process amino acid profiles of cortex, hippocampus, and striatum were not different in seizuring animals when compared to seizure-resistance controls. Of two peptides analyzed, only somatostatin appeared elevated in the cortex 2 hr postictal (143 fmol/mg protein; controls, 123 fmol/mg protein); neuropeptide Y was not affected. A follow up of the time course of cyclic AMP and cyclic GMP showed significant elevations of both substances as a consequence of seizures. Most prominent was a 5.5-fold increase in cyclic GMP in the cerebellum 30 sec after seizure onset.
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PMID:Biochemical events in spontaneous seizures in the Mongolian gerbil. 256 12

The effect of somatostatin (SRIF) on VIP induction of SRIF secretion, cyclic AMP accumulation and 45Ca2+ influx was investigated in cultured diencephalic cells. [D-Trp8]SRIF suppressed VIP-stimulated SRIF release and decreased VIP-stimulated cyclic AMP accumulation in a dose-dependent manner. SRIF-14 blocked basal and VIP-stimulated 45Ca2+ entry into cells. The data suggest that the inhibitory effect of SRIF on VIP-induced SRIF release is partly due to a decrease in Ca2+ entry into cells.
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PMID:Somatostatin inhibition of VIP-induced somatostatin release, cyclic AMP accumulation and 45Ca2+ uptake in diencephalic cells. 256 90

The concept of multifactorial pituitary control is now well established. As in other cell systems, integration of complex messages involves dynamic interactions of receptors and coupling mechanisms. Regulation of adenohypophyseal secretions has been shown to involve cyclic AMP production, the modulation of phosphatidylinositol phosphate breakdown and Ca2+ mobilization. Dopamine, somatostatin and angiotensin II receptors are negatively coupled to adenylate cyclase in anterior pituitary cells. In the case of angiotensin, this effect on adenylate cyclase appears paradoxical since the peptide markedly stimulates prolactin secretion. In fact, angiotensin II also markedly stimulates inositol phosphate production and this effect could account for the stimulated hormone secretion. In addition, dopamine could inhibit inositol phosphate production stimulated by angiotensin II and thyrotropin-releasing hormone. Dopamine and somatostatin also directly modulate voltage-dependent calcium channels, perhaps through a direct coupling with potassium channels. On the other hand, steroids modulate the sensitivity of adenohypophyseal cells to neurohormones by different mechanisms. In the case of somatostatin, it increases the number of specific binding sites, while in the case of dopamine estradiol affects the transduction mechanisms of D2 dopamine receptors. In conclusion, dopamine and somatostatin receptors appear coupled to various transduction mechanisms through pertussis-sensitive G proteins in anterior pituitary cells.
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PMID:Multiple transduction mechanisms of dopamine, somatostatin and angiotensin II receptors in anterior pituitary cells. 256 74


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