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 mechanisms of somatostatin secretion from nerve endings were investigated using the rat median eminence and neurohypophysis in vitro. Determination of total immunoreactive somatostatin content yielded: 36 +/- 2,7 ng per median eminence and 0,74 +/- 0,09 ng per neural lobe. Upon increasing the external potassium concentration a significant rise in somatostatin release from both tissues was observed. (Neural lobe: from 0,86% to 7,4%, median eminence: from 0,09% to 0,47% of total content per 30 minutes). A significant increase in hormone output was also observed following electrical stimulation. The secretory response was abolished whenever external calcium was omitted or replaced by manganese. It is concluded that somatostatin secretion from median eminence and neural lobe in vitro shows two characteristics typical of a neurosecretory process: release upon membrane depolarization and dependence of this process on external calcium.
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PMID:[In vitro somatostatin secretion from the median eminence and the neurohypophysis]. 66 11

Many cells develop enhanced adenylate cyclase activity after prolonged exposure to drugs that acutely inhibit the enzyme and it has been suggested that this adaptation may be due to an increase in Gs alpha. We have treated wild-type and Gs alpha-deficient cyc- S49 mouse lymphoma cells with a stable analogue (SMS 201-995) of the inhibitory agonist somatostatin. After incubation with SMS for 24 h, the forskolin-stimulated cAMP synthetic rate in intact cyc- cells was increased by 76%, similar to the increase found in the wild-type cells. Forskolin-stimulated adenylate cyclase activity in the presence of Mn2+ was also increased in membranes prepared from SMS-treated cyc- cells; however, guanine nucleotide-mediated inhibition of adenylate cyclase activity was not changed despite a small decrease in inhibitory Gi alpha subunits detected by immunoblotting. Pretreatment of cyc- cells with pertussis toxin prevented SMS from inducing the enhancement of forskolin-stimulated cAMP accumulation in intact cells. After chronic incubation of cyc- cells with SMS, exposure to N-ethylmaleimide, which abolished receptor-mediated inhibition of cAMP accumulation, did not attenuate the enhanced rate of forskolin-stimulated cAMP synthesis compared to N-ethylmaleimide-treated controls. These results with cyc- cells demonstrate that an adaptive increase in adenylate cyclase activity induced by chronic treatment with an inhibitory drug can occur in the absence of expression of Gs alpha.
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PMID:Prolonged activation of inhibitory somatostatin receptors increases adenylate cyclase activity in wild-type and Gs alpha-deficient (cyc-) S49 mouse lymphoma cells. 132 4

A phosphoryl protein tyrosine phosphatase (PTPase) activity has been characterized in rat pancreatic acinar membranes using 32P-labeled poly(Glu,Tyr) as substrate. Acinar membranes exhibited a high affinity for the substrate, with an apparent Km of 0.46 microM and an apparent Vmax of 0.9 nmol.mg protein-1.min-1. Acinar membrane PTPase activity displayed specific characteristics of other PTPases; it was inhibited by the inhibitors Zn2+, orthovanadate and by the divalent cations Mn2+ and Mg2+, and was stimulated by the reducing-agent dithiothreitol. It was also inhibited by soybean trypsin inhibitor and stimulated by trypsin. Gel permeation of pancreatic acinar membranes gave a single peak of enzyme activity with an apparent molecular mass of 70 000 Da. Further purification by HPLC on DEAE revealed two peaks of PTPase activity at 120 mM and 180 mM NaCl. These two peaks reacted in a Western-blot procedure with anti-(peptide) serum directed towards conserved domain of PTPase as a common 67-kDa form associated with lower-molecular-mass proteolytic fragments (31-56 kDa). Incubation of pancreatic acini with somatostatin analogues, SMS 201-995 or BIM 23014, resulted in a stimulation of membrane PTPase activity. The stimulation was rapid and transient, with a maximal level reached within 15 min of addition. The two analogs stimulated PTPase activity in a dose-dependent manner with half-maximal activation occurring at 7 pM and 37 pM and maximal activation at 0.1 nM and 0.1-1 nM for SMS 201-995 and BIM 23014, respectively. The stimulated-membrane PTPase activity also eluted at an apparent molecular mass of 70 kDa in gel-permeation chromatography. The two analogs inhibited the binding of [125I-Tyr3]SMS 201-995 to pancreatic acinar membranes with similar relative potencies to that observed on stimulation of PTPase activity. We conclude that pancreatic acinar membranes possess a low-molecular-mass PTPase which is stimulated by somatostatin analogs at concentrations involving activation of membrane somatostatin receptors.
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PMID:Stimulation of a membrane tyrosine phosphatase activity by somatostatin analogues in rat pancreatic acinar cells. 149 47

The development and clinical studies of contrast agents for cross-sectional abdominal imaging presently focus on the diagnosis of liver diseases and suitable oral contrast agents for MR imaging. The well-known paramagnetic agent, gadopentetate dimeglumine is now used for improving the differential diagnosis of liver lesions such as focal nodular hyperplasia in dynamic MR studies. Preclinical studies and initial clinical trials indicate that the new paramagnetic hepatobiliary contrast agent, manganese dipyridoxal diphosphate, might improve the sensitivity of MR imaging in the detection of liver lesions. With respect to dynamic contrast-enhanced CT in the detection of liver lesions, interest has focused on the question of the optimal scanning technique. Promising results have been obtained in initial studies of contrast agents for sonography, called microbubbles. This substance produces good visualization of the vascular status of liver tumors. Nuclear medicine somatostatin receptor imaging may be of special clinical interest because it allows even very small somatostatin-positive metastases to be detected and thus provides specific information for therapy planning in patients with positive scan results. Initial studies have shown that using contrast enhancement with MR imaging of the pancreas improves the contrast between pancreatic tissue and lesions. Manganese dipyridoxal diphosphate is taken up by pancreatic tissue, though the exact mechanism remains to be clarified, and may therefore have potential as a future MR contrast agent for evaluation of the pancreas. A number of oral MR contrast agents have now been tested in larger clinical trials. Both positive and negative oral agents are safe and well tolerated and achieve the aim of reliably delineating the gastrointestinal tract from other organs and pathologies in the abdomen.
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PMID:Contrast materials for cross-sectional imaging of the abdomen. 158 Nov 39

The interaction between somatostatin and acetylcholine, two putative transmitters in the nucleus ambiguus, was investigated on single ambigual neurons in a brainstem slice preparation. Somatostatin reversibly inhibited the nicotinic cholinoceptor-mediated depolarization and inward current induced by acetylcholine. This inhibition persisted in the presence of tetrodotoxin (TTX) or Mn2+. In contrast, somatostatin enhanced both the glutamate-evoked depolarization and spiking discharges generated by current injection. These results suggest that somatostatin exerts a differential action in modulating excitatory inputs to the nucleus ambiguus at the level of postsynaptic receptors.
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PMID:Somatostatin inhibits nicotinic cholinoceptor mediated-excitation in rat ambigual motoneurons in vitro. 167 25

We used rabbit antisera against manganese (Mn)-superoxide dismutase for immunohistochemical studies of localization in the rat neostriatum. Immunostaining was intense in large-sized neurons and several medium-sized neurons, but it was moderate to weak in other cells. Double immunostaining with monoclonal antibody to choline acetyltransferase or somatostatin demonstrated large-sized, Mn-SOD immunoreactive neurons to be cholinergic, and some medium-sized neurons which were intensely immunoreactive for Mn-SOD to contain somatostatinergic.
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PMID:Localization of Mn-superoxide dismutase (Mn-SOD) in cholinergic and somatostatin-containing neurons in the rat neostriatum. 168 20

The tissue-selective binding of the two principal bioactive forms of somatostatin, somatostatin-14 (SS-14) and somatostatin-28 (SS-28), their ability to modulate cAMP-dependent and -independent regulation of post-receptor events to different degrees and the documentation of specific labelling of SS receptor subtypes with SS-28 but not SS-14 in discrete regions of rat brain suggest the existence of distinct SS-14 and SS-28 binding sites. Receptor binding of SS-14 ligands has been shown to be modulated by nucleotides and ions, but the effect of these agents on SS-28 binding has not been studied. In the present study we investigated the effects of adenine and guanine nucleotides as well as monovalent and divalent cations on rat brain SS receptors quantitated with radioiodinated analogs of SS-14 ([125I-Tyr11]SS14, referred to in this paper as SS-14) and SS-28 ([Leu8, D-Trp22, 125I-Tyr25] SS-28, referred to as LTT* SS-28) in order to determine if distinct receptor sites for SS-14 and SS-28 could be distinguished on the basis of their modulation by nucleotides and ions. GTP as well as ATP exerted a dose-dependent inhibition (over a concentration range of 10(-7)-10(-3) M) of the binding of the two radioligands. The nucleotide inhibition of binding resulted in a decrease the Bmax of the SS receptors, the binding affinity remaining unaltered. GTP (10(-4) M) decreased the Bmax of LTT* SS-28 binding sites to a greater extent than ATP (145 +/- 10 and 228 +/- 16 respectively, compared to control value of 320 +/- 20 pmol mg-1). Under identical conditions GTP was less effective than ATP in reducing the number of T* SS-14 binding sites (Bmax = 227 +/- 8 and 182 +/- 15, respectively, compared to 340 +/- 15 pmol mg-1 in the absence of nucleotides). Monovalent cations inhibited the binding of both radioligands, Li+ and Na+ inhibited the binding of T* SS-14 to a greater extent than K+. The effect of divalent cations on the other hand was varied. At low concentration (2 mM) Mg2+, Ba2+, Mn2+, Ca2+ and Co2+ augmented the binding of both T* SS-14 and LTT* SS-28, while higher than 4 mM Co2+ inhibited binding of both ligands. LTT* SS-28 binding was reduced in the presence of high concentrations of Ba2+ and Mn2+ also. Interestingly Ca2+ at higher than 10 mM preferentially inhibited LTT* SS-28 binding and increased the affinity of SS-14 but not SS-28 for LTT* SS-28 binding sites.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Receptor binding of somatostatin-14 and somatostatin-28 in rat brain: differential modulation by nucleotides and ions. 197 Jan 85

We have characterized specific receptors for tetradecapeptide somatostatin (SS-14) of rat brain using 125I-labeled Tyr11-SS-14([125I-Tyr11]SS-14) as radioligand. [125I-Tyr11]SS-14 binding was sensitive to time, pH, temperature and ionic strength of the buffer, and was optimal in 50mM HEPES/KOH buffer, pH 7.5, at 25 degrees C for 60 minutes. Scatchard analysis indicated that the rat forebrain membranes had a single binding site with an apparent dissociation constant (Kd) of 0.522 +/- 0.044 nM and maximum binding capacity (Bmax) was 233 +/- 37 fmol/mg protein (mean +/- SEM). Ca2+, Mg2+, Mn2+ and Co2+ had a significant effect on the specific binding, which indicates that these metal ions might affect somatostatin receptor activity in the brain. Among CNS acting drugs, Ca2+ antagonists, antischizophrenic drugs, antidepressants and anticholinergic drugs had relative effects on [125I-Tyr11]SS-14 bindings to rat cerebral cortex membranes.
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PMID:Biochemical and pharmacological characterization of somatostatin receptors in rat brain. 257 1

Phorbol esters alter cyclic AMP levels in a number of tissues, including the anterior pituitary. We report that membrane preparations from GH3 cells exposed to phorbol esters exhibit decreased vasoactive intestinal peptide (VIP)-stimulated and enhanced forskolin-stimulated adenylate cyclase activity. The responsiveness of adenylate cyclase activity to NaF, guanylyl-imidodiphosphate, and Mn2+ was also reduced by phorbol ester treatment. The ability of somatostatin to inhibit forskolin-stimulated adenylate cyclase activity was reduced while phorbol ester exposure had no apparent effect on somatostatin inhibition of VIP-stimulated adenylate cyclase activity. We suggest that protein kinase C alters at least two distinct components of the adenylate cyclase system. One modification disrupts hormone receptor-Gs interaction (lowering VIP efficacy) and the second perturbation augments the activity of the adenylate cyclase catalytic subunit.
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PMID:Phorbol esters induce two distinct changes in GH3 pituitary cell adenylate cyclase activity. 283 67

Addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) to S49 lymphoma cells (wild type and a cyclic AMP-dependent protein kinase-lacking clone) has little effect alone but doubles accumulation of cyclic AMP in response to isoproterenol. The effect is immediate and has an apparent affinity and order of potency characteristic of the activation of protein kinase C by phorbol esters. Enhancement does not reflect an altered time course of the beta-adrenergic response, enhanced affinity of the cellular beta-receptor for agonist, or decreased degradation and export of cellular cyclic AMP. Reduction of the beta-adrenergic response by somatostatin does not remove the effect of TPA nor does TPA abolish the effect of somatostatin. Phorbol ester enhances cyclic AMP accumulation in response to cholera toxin in wild type and UNC clones but not in H21a or cyc-. TPA also enhances cAMP accumulation in response to forskolin in wild type cells. The effect of TPA is stable to rapid preparation of membranes. In adenylate cyclase assays on membranes from cells treated with TPA, the activation by guanosine 5'-(beta, gamma-imino)triphosphate is enhanced by 40% with no change in lag time; the effect of beta-agonist plus Gpp(NH)p is similarly enhanced; activation by Mn2+ is unchanged. We conclude that phorbol ester facilitates the productive interaction of the alpha subunit of the transducer protein Gs with the catalytic unit of adenylate cyclase, hypothetically via an action of protein kinase C.
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PMID:Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Putative effect of C kinase on alpha s-GTP-catalytic subunit interaction. 285 14


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