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)

To investigate the mechanism of the suppressive action of somatostatin on gastric acid secretion, we determined the somatostatin binding and adenylate cyclase activity on crude membrane fractions of isolated gastric glands of guinea pigs. The binding studies using 125I-Tyr11 somatostatin showed the presence of somatostatin receptors with a single high affinity on crude membrane fractions. The dissociation constant (KD) for somatostatin was 1.05 +/- 0.13 nM, and the number of binding sites (Bmax) was 6.98 +/- 1.27 fmol/mg protein (mean +/- SE, n = 6). The adenylate cyclase activity was increased by histamine, which was completely inhibited by 10(-3) M cimetidine. Somatostatin non-competitively suppressed the histamine-stimulated adenylate cyclase activity in the presence of guanosine 5'-triphosphate (GTP). These results suggest that somatostatin inhibits histamine-stimulated acid secretion through the inhibition of the adenylate cyclase system, via somatostatin receptor and guanine nucleotide binding protein, which is activated by GTP binding.
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PMID:Somatostatin receptors and the effect of somatostatin on histamine-stimulated adenylate cyclase activity in isolated gastric glands of guinea pigs. 257 63

We studied the effect of somatostatin on contractile responses to electrical field stimulation (EFS) in isolated ferret tracheal segments. Somatostatin (up to 10(-5) M) did not change resting tension, but it potentiated the contractile response to EFS dose dependently, with a maximum effect at 10(-6) M. Thus, at a concentration of 10(-6) M, somatostatin significantly decreased the mean log of EFS frequency producing 50% of maximum contraction from a control value of 0.52 +/- 0.07 to 0.24 +/- 0.06 (SE) Hz (P less than 0.01). The potentiating effect of somatostatin (10(-6) M) was not inhibited by hexamethonium, indomethacin, BW755C, pyrilamine, methysergide, or D,Pro2,D,Trp7,9-SP, but it was inhibited by atropine or by the somatostatin antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]. In contrast to EFS-induced contraction, contractions produced by acetylcholine (10(-9) to 10(-3) M) were not affected by somatostatin at a concentration of 10(-6) M. These results suggest that somatostatin potentiates contractions produced by EFS via presynaptic cholinergic mechanisms and probably through a specific somatostatin receptor.
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PMID:Somatostatin potentiates cholinergic neurotransmission in ferret trachea. 257 91

Tumor promoting phorbol esters inhibited the binding of 125I-[Tyr11] somatostatin to isolated acinar cells from guinea-pig pancreas. Maximal inhibition reached 69.7 +/- 5% at 1 microM TPA. Receptor affinity was decreased by 2.5-fold without change in binding capacity. The ability of TPA in inhibiting somatostatin binding was decreased in 30 nM Ca2+ medium, abolished at 4 degrees C or in a membrane preparation. The effect of caerulein, a secretagogue which also caused loss of binding, and that of TPA were not additive. We concluded that TPA inhibits somatostatin binding not by binding directly at the active site of somatostatin receptor. TPA may act at a later point than caerulein via a similar pathway to modulate somatostatin receptor affinity.
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PMID:Tumor promoter inhibition of cellular binding of somatostatin. 258 70

Somatostatin receptors in rat brain, pituitary, and pancreas were labeled with two radioiodinated analogs of somatostatins 14 and 28. Two cyclic analogs of somatostatin, SMS201-995 and cyclo(Ala-Cys-Phe-D-Trp-Lys-Thr-Cys), showed biphasic displacement of binding to somatostatin receptors by these radioligands. In contrast, all other somatostatin analogs, including somatostatin-14, competed for the receptor sites with monophasic displacement of radioligand receptor binding. Thus two types of somatostatin receptors were identified. It was found that the pituitary and pancreas have predominantly one type of somatostatin receptor whereas the brain has both, and that different regions of the brain have various proportions of the two types. These findings suggest methods to characterize other types of somatostatin receptors subserving somatostatin's diverse physiological functions, including a potential role in cognitive function and extrapyramidal motor system control.
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PMID:Two types of somatostatin receptors differentiated by cyclic somatostatin analogs. 285 17

Somatostatin-related peptides act within the central nervous system to influence adrenomedullary epinephrine secretion and thermoregulation. Cysteamine-induced depletion of brain somatostatin-related peptides or central administration of a somatostatin receptor antagonist alters adrenomedullary epinephrine secretion and thermoregulation in a predictable manner. The actions of cysteamine and the somatostatin receptor antagonist are reversed by administration of somatostatins into the central nervous system, supporting the hypothesis that endogenous brain somatostatin-related peptides are involved in the regulation of adrenomedullary epinephrine secretion and thermoregulation.
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PMID:Central nervous system actions of somatostatin-related peptides. 286 33

The binding parameters and distribution of somatostatin receptors were determined in the rat brain using in vitro light microscopic autoradiography. The proteolysis resistant somatostatin analog (des-Ala1-, Gly2-desamino-Cys3Tyr11-dicarba3,14-somatostatin; CGP 23,996) radiolabeled with 125iodine proved to be suitable for the localization of somatostatin receptors. Slide mounted tissue sections showed that 125I-CGP 23,996 bound to the somatostatin receptor with a mean Kd value of 4.0 nM. The mean density of receptors (maximum binding) was determined to be 182 fmol/mg of protein. Both somatostatin and unlabeled CGP 23,996 displayed high-affinity binding for somatostatin receptors with IC50 values of 6 and 5 nM, respectively. The areas containing the highest densities of receptors are the basal amygdaloid nucleus, medial habenular nucleus, stratum oriens and radiatum of CA1 and CA2, and the subiculum. High receptor density can also be found in the deep layers of the cingulate cortex and in the deep layers of temporal cortex. Moderate densities occur in the caudate-putamen, the granule cell layer of the cerebellum, CA3 area of the hippocampus, the molecular layer of the dentate gyrus and in the substantia nigra. Brain areas with low specific binding include the molecular layer of the cerebellum and the corpus callosum, a white matter area.
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PMID:Light microscopic autoradiographic localization of somatostatin receptors in the rat brain. 286 34

A radioiodinated analogue of somatostatin 28, 125I [Leu8,D-Trp22,Tyr25] SS-28, was used to localize and characterize somatostatin binding sites in both human and monkey brain. High-affinity binding sites (approximately 1 nM) were found in cerebral cortex. The highest binding was in cerebral cortex with intermediate binding found in hippocampus, striatum, and amygdala and low binding in hypothalamus and brainstem. There was a rough correlation between somatostatin receptor binding and concentrations of somatostatin-like immunoreactivity (SLI) in human brain. Somatostatin receptors were stable for up to 24 h in an animal model simulating human autopsy conditions and there was no correlation between postmortem interval and receptor binding in human brain. Pharmacologic characterization in human cortex showed that there was a correlation between the inhibition of receptor binding by somatostatin analogues and their known abilities to inhibit growth hormone secretion. These findings demonstrate that a highly specific membrane-associated receptor for somatostatin is present in both monkey and human brain. Examination of somatostatin receptor binding in Alzheimer's disease and Huntington's disease may improve understanding of the role of somatostatin in both these illnesses.
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PMID:Somatostatin binding sites in human and monkey brain: localization and characterization. 286 23

We and others have suggested previously that the binding of somatostatin to its receptors in the pancreas is regulated by not only somatostatin analogs but also cholecystokinin analogs in proportion to their known biological potencies. To clarify the precise mechanism by which unrelated peptides modulate somatostatin binding, the effect of a phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), or a synthetic diacylglycerol analog, 1-oleyl-2-acetylglycerol (OAG), on [125I-Tyr1]somatostatin binding to pancreatic acinar cell membranes was examined. Pretreatment of pancreatic acini for 120 min at 37 degrees C with 100 ng/ml TPA maximally reduced subsequent labeled somatostatin binding to acinar membranes. The inhibitory effect of TPA on the somatostatin binding was dependent on the dose used or the time and temperature of pretreatment. These effects of TPA were almost mimicked by the treatment of acini with OAG. Scatchard analysis of [125I-Tyr1]somatostatin binding demonstrated that the decrease in the labeled somatostatin binding induced by TPA or OAG pretreatment was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. A specifically labeled single band of Mr = 90,000 obtained with a photoaffinity cross-linking study indicates that the somatostatin-binding sites are the same somatostatin receptor as previously described. Moreover, the intensity of the Mr = 90,000 band was dramatically decreased when acini were treated with increasing concentrations of TPA, a finding consistent with TPA-induced decrease in binding capacity. Such an inhibitory effect of TPA was abolished when pretreatment of acini with TPA was performed in the presence of Ca2+-chelating compounds such as EDTA and EGTA or phospholipid-interacting drugs such as chlorpromazine and tetracaine. Interestingly, the combined treatment of TPA and Ca2+ ionophore A23187 caused synergistic inhibition of the subsequent labeled somatostatin binding to acinar membranes, although Ca2+ ionophore itself almost failed to affect the somatostatin binding. These results suggest, therefore, that TPA or OAG can modulate somatostatin binding to its receptors on rat pancreatic acinar cell membranes, presumably through activation of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C); and the activated protein kinase C and intracellular Ca2+ mobilization presumably act to modulate the pancreatic acinar somatostatin receptors synergistically.
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PMID:Phorbol ester or diacylglycerol modulates somatostatin binding to its receptors on rat pancreatic acinar cell membranes. 286

More insight into the biochemical structure and operation of the somatostatin receptor(s) has been gained in recent years from several approaches. The minimal active structure of the receptor(s) has been identified, and active minisomatostatins have been synthesized. High-affinity binding sites (KDS ranging from 0.1 to 1 nM) have been demonstrated in brain and peripheral organs. In pancreas, stomach, and intestine additional low-affinity sites (or states) have been also suggested Furthermore, cytosolic receptors might be present. Binding affinities of synthetic minisomatostatins, somatostatin-14 and somatostatin-28, show different tissue specificities, suggesting the existence of different receptor subtypes. Two possible interactions of somatostatin with stimulus-secretion coupling in secretory cells have been suggested: a direct activation of the GTP-dependent inhibitory subunit of adenylate cyclase and a distal activation of cytosolic phosphoprotein phosphatases.
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PMID:Somatostatin receptors. 287 5

To clarify the precise mechanism by which unrelated peptides, cholecystokinin or carbamylcholine, modulate the somatostatin binding, the effect of a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) or a synthetic diacylglycerol analog, 1-oleyl-2-acetylglycerol (OAG) on [125I-Tyr1]somatostatin binding to pancreatic acinar cell membranes was examined. Pretreatment of pancreatic acini for 120 min at 37 degrees C with 100 ng/ml TPA maximally reduced subsequent labeled somatostatin binding to acinar membranes. The inhibitory effect of TPA on the somatostatin binding was dependent on the dose used, or the time and temperature of pretreatment. These effects of TPA were almost mimicked by the treatment of acini with OAG. Scatchard analysis of [125I-Tyr1]somatostatin binding demonstrated that the decrease in the labeled somatostatin binding induced by TPA or OAG pretreatment was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. A specifically labeled single band of the Mr = 90 K obtained with a photoaffinity cross-linking study indicates that the somatostatin binding sites are the same somatostatin receptor as previously described. Moreover, the intensity of the Mr = 90 K band was dramatically decreased when acini were treated with increasing concentrations of TPA, a finding consistent with TPA-induced decrease in binding capacity. Such an inhibitory effect of TPA was abolished when pretreatment of acini with TPA was performed in the presence of Ca2+ chelating compounds such as EDTA and EGTA. Interestingly, the combined treatment of TPA and Ca2+ ionophore A23187 caused synergistic inhibition of the subsequent labeled somatostatin binding to acinar membranes, although Ca2+ ionophore itself almost failed to affect the somatostatin binding. These results suggest, therefore, that TPA or OAG can modulate somatostatin binding to its receptors on rat pancreatic acinar cell membranes, presumably through activation of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) and the activated protein kinase C and intracellular Ca2+ mobilization presumably act to modulate pancreatic acinar somatostatin receptors synergistically.
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PMID:[Phorbol ester or diacylglycerol modulates somatostatin binding to its receptors on rat pancreatic acinar cell membranes]. 287 6


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