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)

Calcitonin gene-related peptide is a putative neurotransmitter of central and peripheral nervous systems which coexists with acetylcholine in motor nerve terminals and exerts multiple effects on skeletal muscle, suggesting a trophic role for this neuropeptide. Using radiolabeled calcitonin gene-related peptide as a probe in a specific binding assay, we have characterized calcitonin gene-related peptide binding sites on chick skeletal muscle membranes. Binding is time-dependent, saturable and reversible. Scatchard analyses revealed two classes of sites: high-affinity sites with a KD value of 62 pM, and low-affinity sites with a KD value of 3.3 nM. The maximal number of sites is, respectively, 22 and 155 fmol/mg protein for high- and low-affinity binding sites. Specific binding was not affected by the presence, in excess, of other neuropeptides such as salmon calcitonin or somatostatin or vasoactive intestinal polypeptide. Affinity of the binding site for calcitonin gene-related peptide was decreased in the presence of 5'-guanylyl-imidodiphosphate, suggesting a physiological coupling of calcitonin gene-related peptide receptor to a GTP binding protein. In a developmental study of chick muscle, we found the highest activity of calcitonin gene-related peptide binding sites in 11-14 day embryos, following a pattern of evolution similar to that of acetylcholine receptors (constant ratio of 12 acetylcholine receptors per calcitonin gene-related peptide binding site). However, both receptors appear differentially regulated: while the number of acetylcholine receptors increases 5-16-fold after denervation, calcitonin gene-related peptide binding sites slightly diminish in number. These results are discussed in terms of the physiological significance of calcitonin gene-related peptide binding sites on chick skeletal muscle membrane.
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PMID:Characterization and developmental evolution of a high-affinity binding site for calcitonin gene-related peptide on chick skeletal muscle membrane. 165 62

In AtT-20 cells somatostatin inhibits the secretion of adrenocorticotropic hormone (ACTH) through the activation of GTP binding proteins (G proteins) linked to second messengers such as calcium and cyclic AMP (cAMP). Recently, it has been proposed that there may be G proteins that regulate directly the exocytotic machinery. We have investigated whether somatostatin could inhibit secretion at a step distal to second messengers through a GTP binding protein. For these studies two experimental paradigms were used: (1) intact cells stimulated by calcium ionophores and (2) digitonin-permeabilized cells exposed to buffers of increasing Ca2+ concentrations. Somatostatin inhibited by 70% the ACTH release caused by the calcium ionophore ionomycin without modifying the ionophore-induced elevation in cytosolic [Ca2+]. This effect was cAMP independent because (1) it was observed in the presence of high concentrations of membrane-permeant cAMP analogues, and (2) it was not accompanied by a change in cAMP levels. The effect was also independent of the levels of activators of protein kinase C because it could be produced in the presence of high concentrations of phorbol esters. The action of somatostatin was prevented by pertussis toxin. In digitonin-permeabilized AtT-20 cells somatostatin inhibited release induced by calcium buffers in a GTP-dependent manner. These two observations indicate the involvement of a G protein. It is proposed that a G protein coupled to somatostatin receptors inhibits the intracellular machinery of secretion at a step distal to second messengers, perhaps at the exocytotic site.
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PMID:Evidence that receptor-linked G protein inhibits exocytosis by a post-second-messenger mechanism in AtT-20 cells. 196 44

Currents through single-ion channels were recorded in the cell-attached configuration from locus ceruleus neurons enzymatically dissociated from newborn rats. When the selective mu opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol was in the patch-clamp electrode, unitary inward currents were observed with conductance of approximately 45 pS (measured at zero pipette potential, with 150 mM potassium in the recording electrode). Long silences, lasting many seconds to minutes, separated periods of activity of similar durations. Within such activity periods the distribution of closed times of the channels was best fitted by the sum of two exponential functions (time constants approximately 1 and 30 ms), and the durations of channel openings were fit by a single exponential function; mean open time increased from 2 to 120 ms as agonist concentration increased. Channel activity was not seen when high concentrations of opioids were applied to the neuron outside the patch-clamp recording electrode, indicating intimate coupling between receptor and potassium channel. Unitary currents with similar properties were also seen when pipettes contained alpha 2 adrenoceptor agonists or somatostatin. Taken with previous findings, the results indicate that mu opioid receptors, alpha 2 adrenoceptors, and somatostatin receptors can couple directly to membrane potassium channels through the local intermediary action of a GTP binding protein.
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PMID:Single potassium channels opened by opioids in rat locus ceruleus neurons. 256 72

We studied the interaction between somatostatin receptors and inhibitory GTP binding protein in rat cerebrocortical membranes. Guanine nucleotides reduced [125I-Tyr1] somatostatin binding to cerebrocortical membranes in a dose-dependent manner with rank order of potency being guanyl-5'-yl-imidodiphosphate (Gpp(NH)p) greater than GTP greater than GMP. Maximum reduction of the binding to 32% of control was observed in the presence of 10(-5) M Gpp(NH)p. Scatchard analysis of the labeled somatostatin binding revealed that the decrease in the binding by Gpp(NH)p was due to the decrease in the binding affinity for somatostatin. Divalent cations, such as Mg++, Mn++, and Ca++, caused an increase in labeled somatostatin binding to membranes with the maximum binding observed at a concentration of 10, 10, 1 mM, respectively. However, Na+ decreased a labeled somatostatin binding in a dose-dependent manner, and half maximum inhibition of the binding was observed at 10 mM Na+. Moreover, Gpp(NH)p and Na+ lowered labeled somatostatin binding in an additive fashion. When cerebrocortical membranes were treated at 37 degrees C for 40 min with various concentrations of Islet-Activating-Protein (IAP), which had been preactivated with dithiothreitol, subsequent labeled somatostatin binding to the membranes was decreased in a dose-dependent manner. 30 micrograms/ml IAP treatment caused a decrease in the binding to 50% of control, which was characterized by the decreased binding affinity without a significant change in the binding capacity. Furthermore, exposure of IAP plus NAD to cerebrocortical membranes caused ADP-ribosylation of a membrane protein with Mr = 41,000 on autoradiogram. Such an IAP treatment of cerebrocortical membranes abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in adenylate cyclase activity. These results suggest that somatostatin receptors in the brain couple to inhibitory GTP binding protein, which mediates adenylate cyclase inhibition by somatostatin.
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PMID:[Coupling of inhibitory GTP binding protein to somatostatin receptors on rat cerebrocortical membranes]. 257 11

The molecular mechanisms of somatostatin (SRIF) desensitization were investigated in the anterior pituitary tumor cell line AtT-20. Previous studies have shown that pretreatment of AtT-20 cells with SRIF analogs desensitizes the cells to SRIF inhibition of hormone release, cyclic AMP formation and calcium influx. This desensitization may involve a change in the properties of the SRIF receptors. Pretreatment of AtT-20 cells with Trp8-SRIF reduced the binding of the SRIF analog [125I]CGP 23996 (des-Alal, Gly2-[desamino-Cys3, Tyr11]-3, 14-dicarbasomatostatin) to AtT-20 cell membranes. The loss of [125I]CGP 23996 binding was dependent on the time of Trp8-SRIF treatment and was reversible. The ability of GTP analogs to inhibit [125I]CGP 23996 binding was reduced after Trp8-SRIF treatment, suggesting that the SRIF receptor and the inhibitory G proteins become uncoupled during desensitization. This is indicated further by the decrease in SRIF stimulation of GTPase activity and SRIF inhibition of forskolin-stimulated adenylyl cyclase activity in desensitized membranes. The reduction and recovery of SRIF inhibition of adenylyl cyclase activity after Trp8-SRIF pretreatment has a similar time course as the changes in [125I]CGP 23996 binding. GTP inhibition of forskolin-stimulated adenylyl cyclase activity is also reduced in SRIF-desensitized membranes. The loss of the GTP effect occurs rapidly and does not fully recover after Trp8-SRIF pretreatment. The levels of ADP-ribosylation of inhibitory GTP binding protein, the relative quantity of the alpha subunits of the inhibitory G proteins and their electrophoretic mobility after 2-dimensional gel electrophoretic analysis, are not altered in SRIF-desensitized membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristics of somatostatin desensitization in the pituitary tumor cell line AtT-20. 290 14