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)

GH4C1 cells are a clonal strain of rat pituitary tumor cells which synthesize and secrete prolactin and growth hormone. Somatostatin, a hypothalamic tetradecapeptide, inhibits the release of growth hormone and, under certain circumstances, also prolactin from normal pituitary cells. We have prepared [125I-Tyr1]somatostatin (approximately 2200 C1/mmol) and have shown that this ligand binds to a limited number of high affinity sites on GH4C1 cells. Half-maximal binding of somatostatin occurred at a concentration of 6 x 10(-10) M. A maximum of 0.11 pmol of [125I-Tyr1]somatostatin was bound per mg of cell protein, equivalent to 13,000 receptor sites per cell. The rate constant for binding (kon) was 8 x 10(7) M(-1) min(-1). The rate constant for dissociation (koff) was determined by direct measurement to be 0.02 min(-1) both in the presence and absence of excess nonradioactive somatostatin. Binding of [125I-Tyr1]somatostatin was not inhibited by 10(-7) M thyrotropin-releasing hormones. Substance P, neurotensin, luteinizing hormone-releasing hormone, calcitonin, adrenocorticotropin, or insulin. Of seven nonpituitary cell lines tested, none had specific receptors for somatostatin. Somatostatin was shown to inhibit prolactin and growth hormone production by CH4C1 cells. The dose-response characteristics for binding and the biological actions of somatostatin were essentially coincident. Furthermore, among several clonal pituitary cell strains tested, only those which had receptors for somatostatin showed a biological response to the hormone. We conclude that the characterized somatostatin receptor is necessary for the biological actions of somatostatin on GH4C1 cells.
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PMID:Characterization of functional receptors for somatostatin in rat pituitary cells in culture. 21 Jan 85

Utilizing histones as a substrate and measuring the production of labelled phosphoserine from [gamma 32P-ATP], cAMP stimulated protein kinase activity was found in islet and anterior pituitary secretory vesicles. Cyclic AMP (5 X 10(-7)m)stimulated islet secretory vesicle protein kinase activity as evidenced by a net increase of 32P incorporation into phosphoserine 7.35 +/- 1.68 pmoles/micrograms, (P LESS THAN 9001). Somatostatin (0.1 ng/microgram) decreased 32P phosphoserine production from 10.64 +/- 1.72 to 5.61 +/- 1.26 pmoles/microgram (Pless than .01) by suppressing cAMP stimulated protein kinase activity. In pituitary secretory vesicles, cAMP (5 X 10(-6M) increased 32P incorporation into TCA precipitable protein from 127.3 +/- 8.6 to 202.6 +/- 12.5 pmoles/microgram, P less than .001. With somatostatin (0.2 ng/microgram) there was 55.25+/- 1.95% inhibition of cAMP stimulated protein kinase activity, (P LESS THAN .001). Somatostatin did not inhibit cAMP stimulated protein kinase activity in erythrocyte membrane ghosts nor did somatostatin inhibit the partially purified cAMP dependent protein kinase from cardiac muscle. These data suggest that either (1) a specific somatostatin sensitive dependent protein kinase is present in islet and anterior pituitary secretory vesicles or (2) that a somatostatin receptor is present in these tissues which allows somatostatin to act selectively at these sites. Somatostatin may act by inhibiting the cAMP dependent protein kinase enzme in certain key tissues or subcellular organelles.
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PMID:Somatostatin: selective inhibition of cyclic AMP stimulated protein kinase. 22 50

1. The effect of somatostatin and eighteen somatostatin analogues on pentagastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogues are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. 2. The ID50 for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 microgram kg-1 hr-1 was found to be 1.29 +/- 0.13 n-mole kg-1 hr-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. 3. D-Phe6, D-Phe7, D-Thr10, D-Thr12 and D-Phe6-D-Trp8 analogues all show low biological activity against the secretion of gastric acid and pepsin, growth hormone, insulin and glucagon. None of these analogues are antagonists of the cyclic-somatostatin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. 4. The analogues under investigation show parallel changes in activity against gastric and growth hormone secretion, suggesting a similarity between the gastric and growth hormone receptors for somatostatin. 5. D-Cys14 analogues are equipotent with or have a greater potency than cyclic-simatostatin in inhibiting the secretion of gastric acid, growth hormone and glucagon but show low insulin inhibiting activity.
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PMID:Structure-activity relationships of eighteen somatostatin analogues on gastric secretion. 34 35

We report the case of a patient with Verner-Morrison syndrome due to a malignant MEN I-associated vipoma. Marked tumor-associated hypercalcemia could be treated successfully with somatostatin analogues prior to surgical therapy of the pancreatic tumor. Sixteen months after extirpation of the primary tumor recurrent tumor growth was diagnosed; at this time the patient was clinically asymptomatic and had no abnormal laboratory test results. Liver metastases and local metastases were identified using somatostatin receptor scintigraphy. We report and discuss the use of somatostatin in the treatment of tumor-associated symptoms in endocrine tumors and the possibility of identifying endocrine tumors by means of somatostatin receptor scintigraphy.
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PMID:[Somatostatin in preoperative therapy and postoperative diagnosis of a patient with Verner Morrison syndrome]. 128 41

The somatostatin analogue octreotide (SMS 201-995) inhibits secretion and growth of certain tumor cells, and current efforts are directed toward the elucidation of its mode of antiproliferative action. In this study, the effect of octreotide on the growth of ZR-75-1 human breast cancer cells has been characterized in immunodeficient nude mice and in cell culture. These results have been related to the expression of somatostatin receptors in vivo and in vitro. Continuous infusion of 10 micrograms/kg/h of octreotide yielded plasma levels of 5.7 ng/ml and elicited highly significant growth inhibitory effects on solid ZR-75-1 breast tumors in nude mice. After 2 and 4 weeks of treatment, tumor volumes in the octreotide group were 39.1 and 36.7% of those of control animals treated with vehicle, respectively. Autoradiographic studies demonstrated that 8 of 12 ZR-75-1 tumors studied were somatostatin receptor positive. When ZR-75-1 tumor cells were exposed in vitro to nanomolar concentrations of octreotide, a dose-dependent inhibition of cell growth was observed in the presence of 5% fetal calf serum or under serum-free conditions using epidermal growth factor, insulin-like growth factor type I, or insulin as growth stimulus. In parallel receptor-binding experiments, ZR-75-1 cells were shown to express specific high-affinity somatostatin receptors (Kd value = 0.9 nM, Bmax = 6000 sites/cell). From these experiments, we conclude that octreotide is a powerful inhibitor of ZR-75-1 tumor cell growth in nude mice and in culture. This inhibitory action of octreotide and the presence of somatostatin receptors on ZR-75-1 tumor cells in vitro and in vivo suggest a direct, somatostatin receptor-mediated effect of octreotide.
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PMID:Antiproliferative effects of the somatostatin analogue octreotide (SMS 201-995) on ZR-75-1 human breast cancer cells in vivo and in vitro. 132 89

The gene encoding a novel mouse somatostatin receptor termed mSSTR3 was isolated and characterized. The sequence of mSSTR3 shows 46 and 47% identity with mSSTR1 and mSSTR2, respectively. mSSTR3 binds somatostatin-14 and somatostatin-28 with high affinity, but shows very low affinity for the somatostatin analogs MK-678 and SMS-201-995. In addition, mSSTR3 is coupled to pertussis toxin-sensitive G proteins and mediates somatostatin inhibition of forskolin-stimulated and dopamine D1 receptor-stimulated cAMP formation, indicating that it is coupled to adenylylcyclase. The pharmacological properties of mSSTR3 and its ability to couple with adenylylcyclase distinguish SSTR3 from the other cloned somatostatin receptors and indicates that it mediates biological functions different from SSTR1 or SSTR2. In situ hybridization indicates that SSTR3 mRNA is widely distributed in the mouse brain, and its expression in the nucleus of the lateral olfactory tract and in the piriform cortex, the primary olfactory cortex in the rodent brain, suggests that SSTR3 may participate in the processing and modulation of primary sensory information.
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PMID:Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylylcyclase. 132 99

We previously reported the cloning of two distinct somatostatin receptor (SSTR) subtypes, SSTR1 and SSTR2. Although both SSTR1 and SSTR2 bound somatostatin specifically and with high affinity, neither was coupled to adenylyl cyclase, a major cellular effector of somatostatin's actions. Here we report the cloning and functional characterization of a third member of the SSTR family. Human SSTR3 is a protein of 418 amino acids and has 45% and 46% identity with human SSTR1 and SSTR2, respectively. RNA blotting studies showed that SSTR3 mRNA could be readily detected in brain and pancreatic islets. The pharmacological properties of human SSTR3 were characterized by transiently expressing the human SSTR3 gene in COS-1 cells. Membranes from cells expressing human SSTR3 bound the somatostatin agonist [125I]CGP 23996 specifically and with high affinity, with a rank order of potency of somatostatin-28 = CGP 23996 > somatostatin-14 > SMS-201-995. Studies using cells transiently coexpressing the human dopamine D1 receptor and human SSTR3 showed that somatostatin was able to inhibit dopamine-stimulated cAMP formation in a dose-dependent manner, indicating that SSTR3 was functionally coupled to adenylyl cyclase. These results indicate that the diverse biological effects of somatostatin are mediated by a family of receptor with distinct, but overlapping, tissue distributions, unique pharmacological properties, and potentially different functions.
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PMID:Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. 133 45

We have previously reported that somatostatin may reduce tumour cellular proliferation in patients with colorectal carcinoma. However, it is not known what proportion of primary colorectal cancers express somatostatin receptors. We have therefore evaluated somatostatin receptor status in 50 primary colorectal cancers. Twelve (24%) of the cancers were shown to be somatostatin receptor positive. There was no correlation between receptor status and tumour stage or grade.
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PMID:Somatostatin receptors in human colorectal cancer. 134 94

Using radiolabeled microspheres, spinal cord blood flow was measured after spinal subarachnoid injections of 3.1- to 12.5-nmol doses of somatostatin through either indwelling i.t. catheters or acutely inserted intervertebral needles. With either injection technique, somatostatin caused significant dose-dependent reductions in thoracic and lumbosacral blood flow that could be partially blocked by a 5-min preinjection of the somatostatin receptor antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)], which has previously been shown to block the hindlimb flaccidity produced by these doses of somatostatin in conscious rats. The duration of these blood flow changes were appreciably less in the rats injected through indwelling i.t. catheters. Somatostatin-induced reductions in spinal cord perfusion were accompanied by transient pressor responses, reduced cardiac output, 3-fold increases in spinal cord cerebrospinal fluid lactic acid concentrations and breakdown of the blood-spinal cord barrier, as reflected by significantly increased extravasation of [125I]bovine serum albumin. By 24 hr postinjection, a 12.5-nmol dose of somatostatin caused appreciable spinal cord cellular injury, as evidenced by significant elevations in cerebrospinal fluid concentrations of lactate dehydrogenase. After topical application to exposed pial vessels of the parietal cortex, comparable doses of somatostatin caused immediate intense dose-related arteriolar vasospasm and subsequent extravasation of the visible macromolecular tracer Evans blue dye. We conclude that somatostatin has significant vasoconstrictory effects on the blood vessels of the brain and spinal cord of the rat that must be recognized and appreciated when studying its neuropharmacological actions in vivo.
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PMID:Somatostatin causes vasoconstriction, reduces blood flow and increases vascular permeability in the rat central nervous system. 134 70

A somatostatin receptor isolated from GH4C1 rat pituitary tumor-derived cells was cleaved with cyanogen bromide or cyanogen bromide+trypsin to obtain sequenceable fragments. Five unique amino acid sequences ranging from 6 to 27 amino acid residues were obtained. The sequence was identical to sequence recently reported for one of two somatostatin receptors cloned from human pancreas [Yamada et al., (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 251-255] except for a single valine to isoleucine substitution. This is the first report of amino acid sequence from a purified somatostatin receptor.
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PMID:Partial amino acid sequence of a somatostatin receptor isolated from GH4C1 pituitary cells. 134 34


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