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 effect of chronic administration of SMS 201-995, a long acting analogue of somatostatin, has been studied in 30 acromegalic patients (pts). CT-scan showed pituitary adenoma in 20/30 pts, empty sella in 9/30 pts and no sign of pituitary tumor in one case. SMS 201-995 was administered subcutaneously every 8 hours at the daily dose of 150-900 micrograms. Blood samples for GH, insulin and blood glucose were taken hourly from 04:00 to 20:00 h before treatment, after 15 days and then monthly or fortnightly. IGF-I plasma levels were assayed at 08:00 h in the same day as GH determinations. CT-scan controls were carried out after 12-24 months of treatment in 16/20 pts. GH plasma levels were normalized in 16/30 pts after 0.5-9 months of SMS treatment, whereas in 14/30 pts they were reduced by about 50%. In 10/16 pts the CT-scan examination showed a shrinkage of the tumor size of 20-55%, while no variation of the tumor mass was observed in the 2 pts. In conclusion our data show that SMS 201-995 is a very effective medical treatment in acromegalic patients.
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PMID:Medical management of acromegaly: effects of SMS 201-995 in 30 patients. 236 59

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).
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PMID:Acromegaly in 14 cats. 240 66

Somatostatin and carbachol receptors are believed to be negatively coupled to adenylate cyclase in AtT-20 mouse pituitary tumor cells by an inhibitory guanine nucleotide-binding regulatory subunit. Activation of these receptors causes inhibition of cyclic AMP synthesis and adrenocorticotropin (ACTH) secretion stimulated by a variety of hormones. Secretion in response to several pharmacological agents, which do not increase AtT-20 cyclic AMP levels, is also antagonized by both somatostatin and carbachol. Inasmuch as ACTH secretion in response to all stimulants is dependent on extracellular calcium, the possibility that somatostatin and carbachol block calcium entry was investigated by observing the effects of these agents on the activity of the calcium channel activator, BAY-K-8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4- (2-trifluoromethylphenyl)-pyridine-5-carboxy-late] in AtT-20 cells. In first characterizing the effect of BAY-K-8644, it was noted that the channel agonist at 10(-10) to 10(-6) M itself rapidly increased basal ACTH secretion; higher concentrations (10(-4) M) reduced basal, (-)-isoproterenol, phorbol ester, 8-Br-cAMP and K+-stimulated secretion. BAY-K-8644 did not alter basal formation of cyclic AMP. The secretory response to BAY-K-8644 was dependent on extracellular calcium, and was inhibited by the calcium channel antagonist, nifedepine. When coapplied with (-)-isoproterenol, phorbol ester and 8-Br-cAMP, at a concentration which optimally stimulated ACTH secretion, BAY-K-8644 had an additive effect; the secretory responses to K+ (50 mM) or the calcium ionophore, A-23187, on the other hand, were potentiated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of adrenocorticotropin secretion from AtT-20 cells by the calcium channel activator, BAY-K-8644, and its inhibition by somatostatin and carbachol. 241 8

Somatostatin is a neurohormone peptide that inhibits a variety of secretory responses in different cell types. We have investigated the effects of somatostatin on calcium current and intracellular free calcium in AtT-20 cells, a pituitary tumor line in which the inhibitory actions of this peptide have been well characterized. At concentrations similar to those that inhibit adrenocorticotropic hormone (ACTH) release, somatostatin and its analogs reduced the levels of intracellular free calcium (as measured by the Quin-2 technique). Nifedipine and other blockers of voltage-dependent calcium channels also reduced cytosolic calcium levels. The effects of somatostatin and nifedipine were not additive, suggesting that somatostatin might inhibit calcium channels. Experiments using the whole-cell patch-clamp technique showed that somatostatin reduces voltage-dependent calcium current. The effects of somatostatin on cytosolic calcium and calcium current appear to be independent of its ability to reduce secretagogue-stimulated cAMP accumulation in these cells. We propose that the somatostatin-induced decrease in cytosolic calcium concentrations and the voltage-dependent calcium current are one of the mechanisms by which somatostatin suppresses ACTH release in AtT-20 cells.
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PMID:Somatostatin, an inhibitor of ACTH secretion, decreases cytosolic free calcium and voltage-dependent calcium current in a pituitary cell line. 243 73

The effect of pertussis toxin on somatostatin-induced K+ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K+ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma 1, 0/10 in adenoma 2). Spontaneous action potentials, K+, Na+, and Ca2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [32P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.
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PMID:Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells. 244 Mar 14

Regulation of GH gene expression by GRF involves cAMP as a second messenger. We have demonstrated that a 500-basepair fragment of the human GH (hGH) gene 5' flanking region can confer cAMP inducibility upon the chloramphenicol acetyltransferase transcription unit in transient transfections of rat pituitary tumor cells treated with forskolin, an activator of adenyl cyclase. The same hGH construct is not induced by forskolin in nonpituitary-derived cells. Experiments with hGH deletion constructs reveal that binding sites for transcription factor AP-2 and the pituitary-specific factor GHF-1 are not required for forskolin stimulation, but that GHF-1 may potentiate the effect. RNA analyses reveal that forskolin also stimulates accumulation of transcripts initiated at the hGH promoter. Other agents that elevate cAMP levels also stimulate hGH expression. Since the hGH 5' flanking region contains no sequences homologous to the cAMP-responsive element of the somatostatin gene, and the AP-2 sites do not appear to be required for the forskolin response, these results suggest that a novel cAMP-responsive element exists within 82 basepairs upstream from the transcriptional start of the hGH gene and that hGH regulation by GRF may involve interaction between a tissue-specific element and a cAMP-inducible element.
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PMID:Induction of human growth hormone promoter activity by the adenosine 3',5'-monophosphate pathway involves a novel responsive element. 254 55

The marked pituitary tumor shrinkage achieved by continuous sc infusion (CSI) of the long-acting somatostatin analog octreotide in one acromegalic patient led us to treat 16 other acromegalic patients for up to 24 months by CSI. This therapy, given in doses ranging from 100-600 micrograms/day, resulted in normalization of the mean daily serum GH (mGH) and insulin-like growth factor I levels in 9 of the 17 patients (53%). In 7 patients, mean daily serum GH decreased but not to normal; 3 of these patients had hyperprolactinemia which was not influenced by octreotide. One patient was completely unresponsive. In contrast to the biochemical results, 80% of the patients had marked clinical improvement. Side-effects consisted of slightly impaired carbohydrate tolerance in 2 patients and cholelithiasis in 2 patients. Pituitary tumor size decreased in only 3 patients; in 1 of them visual field defects disappeared rapidly. These results suggest that octreotide treatment may prove beneficial before surgery in patients with macroadenomas, although its efficacy varies widely. Potential responsivity can usually be determined by a short course (24 h) of CSI of octreotide.
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PMID:Long term effects of continuous subcutaneous infusion of the somatostatin analog octreotide in the treatment of acromegaly. 256 13

We reported a case of sporadic multiple endocrine neoplasia type 1, with multiple insulinoma, parathyroid adenoma, and pituitary tumor. Measurement of hormone contents and immunohistochemical studies of the pancreatic tumors showed that the tumors contained insulin, glucagon, somatostatin, and pancreatic polypeptide. Furthermore, the concentrations of these hormones were different in each tumor. Insulin extracted from the pancreatic tumors analyzed by reversed-phase high performance liquid chromatography revealed no structural abnormalities. On the other hand, in gel filtration evaluation of the extract of the parathyroid adenoma, it was found that the tumor extract contained a macromolecular parathyroid hormone (molecular weight 20,000 to 25,000).
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PMID:A case of multiple endocrine neoplasia (MEN) type 1; the immunohistochemical and ultrastructural studies of its tumors and the analysis of hormones in tumor extracts. 256 30

Previous studies have shown that somatostatin receptors on AtT-20 and GH3 pituitary tumor cells show relative preference for binding somatostatin-28 (S-28) and somatostatin-14 (S-14), respectively. Here we have attempted to determine whether this selectivity can be explained by molecular heterogeneity of the receptor. Cells were incubated with [125I-Tyr11]S-14, [125I-Leu8-D-Trp22,Tyr25]S-28, and [125I-Tyr3]SMS, and the bound ligand was chemically cross-linked with bis-[2-succinimido-oxycarbonyloxy)ethyl]sulfone, disuccinimidyl suberate, or dithiobis (succinimidyl propionate). The solubilized cross-linked material was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. [125I-Tyr11]S-14 labeled three specific receptor proteins of 57K, 42K, and 27K mol wt in AtT-20 cells. The relative proportions of the protein bands were unaltered by the use of whole cells or cell membranes or by the inclusion of dithiothreitol or antiproteolytic agents. With both [125I-Tyr11]S-14 and [125I-LTT]S-28, the 57K protein constituted the major labeled component, representing 70-75% of the total cross-linked proteins. Labeling of the three protein species by [125I-Tyr11]S-14 and [125I-LTT]S-28 was inhibited by both S-14 and S-28 in a dose-dependent manner. S-28 was 10-20 times more potent than S-14 for inhibiting the labeling by both ligands of the principal receptor species of 57K. By contrast, when a radioiodinated derivative of the octapeptide analog octreotide ([125I-Tyr3]SMS) was used as ligand, the 27K protein was preferentially labeled, whereas the 57K and 42K bands were detected only as minor components. Labeling of GH3 cells with [125I-Tyr11]S-14 and [125I-LTT]S-28 revealed three cross-linked proteins of 57K, 42K, and 27K mol wt similar to those observed in AtT-20 cells. However, in this cell line the 27K protein, not the 57K species, was the dominant component identified with these two ligands, comprising 40-50% of the total cross-linked proteins. These results suggest that there are three somatostatin receptor proteins of 57K, 42K, and 27K in pituitary cells. In AtT-20 cells, the 57K protein constitutes the major receptor protein labeled by [125I-Tyr11]S-14 and [125I-LTT]S-28, whereas the 27K protein is the major species labeled by [125I-Tyr3]SMS. The 27K, not the 57K, moiety is the principal receptor form in GH3 cells. Such ligand- and tissue-selective binding by the somatostatin receptor provides strong evidence for receptor molecular heterogeneity.
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PMID:Evidence for multiple protein constituents of the somatostatin receptor in pituitary tumor cells: affinity cross-linking and molecular characterization. 256 26

Intracellular ionized Ca2+ concentration was measured in clonal mouse anterior pituitary tumor cells with the fluorescent Ca2+ indicator Quin-2. In control physiological solution, free cytoplasmic Ca2+ concentration was found to be 139 +/- 11 nM. Replacement of 50 mM NaCl by 50 mM KCl in the extracellular fluid caused a 29 mV depolarization and a 4.2-fold increase in the concentration of free cytoplasmic Ca2+. Under comparable depolarizing conditions, a specific influx of 2.66 nmole of 45Ca2+ per mg protein was detected 1 min after addition of high K+, accompanied by a marked increase in the initial rate of beta-endorphin secretion. In the absence of external Ca2+, depolarization by K+ produced little or no increase in either intracellular free Ca2+ or hormone release. Incubation of AtT-20/D16-16 cells in the secretagogue norepinephrine led to a depolarization accompanied by an increase in spontaneous action potential frequency and a marked elevation in cytosolic Ca2+ concentration. Exposure of cells to somatostatin, an inhibitor of hormone release, led to only transient decreases in burst frequency and no significant reduction in intracellular Ca2+ levels. These results indicate that in addition to intracellular Ca2+, other factors also control secretory activity in AtT-20/D16-16 anterior pituitary cells.
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PMID:Intracellular calcium and hormone secretion in clonal AtT-20/D16-16 anterior pituitary cells. 257 58


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