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)

Recent evidence suggests that of calcitonin (CT) and parathyroid hormone (PTH) is controlled by factors other than the ambient serum calcium concentration. We studied the effects of infusions of four neuroendocrine modulators upon CT and PTH levels: isoproterenol (beta-adrenergic agonist), methoxamine (alpha adrenergic agonist), prostaglandin E2, and somatostatin. Isoproterenol was a consistent secretagogue for both hormones. Maximal CT increments during isoproterenol infusion in normal subjects were 13 +/- 2 pg/ml (mean +/- SEM, n = 6, P less than 0.001; basal, 26 +/- 5). Maximal increments in PTH were 113 +/- 22 pg/ml (P less than 0.01, n = 6; basal, 430 +/- 11). Infusions of methoxamine increased CT by 13 +/- 5 pg/ml (n = 5, P less than 0.05; basal, 43 +/- 13), but had no effect on PTH. The means of the maximal CT increments during isoproterenol (21 +/- 8 pg/ml) and methoxamine infusion (28 +/- 11 pg/ml) were not statistically different from those achieved by acute elevations of serum calcium levels within the physiological range (41 +/- 23 pg/ml). Infusions of somatostatin and prostaglandin E2 had no or only transient effects on basal or stimulated CT or PTH levels. Our data suggest that adrenergic input modulates CT and PTH secretion in humans independently of changes in serum calcium.
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PMID:Neuroendocrine modulation of calcitonin and parathyroid hormone in man. 4 60

This study evaluated the effect of somatostatin on immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) secretion in vivo in rats and monkeys and on iPTH secretion in vitro by normal bovine parathyroid tissue and by a human parathyroid adenoma. Somatostatin infusion promptly (within 0.5 h) suppressed both iPTH and iCT in both species studied in vivo, the suppression being progressive during the infusion period. In in vitro studies, somatostatin caused significant dose-related decreases in basal, low Ca-stimulated, and high Ca-suppressed PTH secretion from normal bovine parathyroid tissue and from basal and low Ca-stimulated PTH secretion from a human parathyroid adenoma. Therefore, somatostatin 1) suppresses both PTH and CT secretion in vivo; 2) acts directly on the parathyroid cell and presumably directly on the C-cell also; 3) acts upon normal and adenomatous parathyroid tissue; 4) suppresses basal, low Ca-stimulated and high Ca-suppressed PTH secretion; and 5) has a dose-related effect. The possible role of somatostatin in the physiological control of PTH and CT secretion (and therefore in Ca homeostasis), and in the pathogenesis of abnormalities of Ca homeostasis, requires further evaluation.
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PMID:Effect of somatostatin on parathyroid hormone and calcitonin secretion. 10 71

Our previous in vitro and in vivo studies demonstrated that exogenous somatostatin inhibited secretion of both parathyroid hormone (PTH) and calcitonin (CT). This study evaluates the possible role of endogenous somatostatin in PTH and CT secretion. Rats receiving somatostatin antiserum i.v. had significantly greater circulating levels of serum immunoreactive PTH (iPTH) and CT (iCT) than rats receiving normal rabbit serum. In in vitro studies with bovine parathyroid tissue, the addition of somatostatin antiserum to the medium significantly increased PTH secretion from basal, low calcium-stimulated and high calcium-suppressed parathyroid tissue. These combined observations strongly suggest that endogenous somatostatin must have a suppressive effect on PTH and CT secretion. The in vitro observations with isolated parathyroid tissue suggest that somatostatin is synthesized by cells within this tissue. These data strongly suggest that somatostatin is a locally-synthesized hormone that has a role in modulation of both PTH and CT secretion.
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PMID:Role of endogenous somatostatin in the secretion of parathyroid hormone and calcitonin. 48 Dec 22

The effect of somatostatin on plasma parathyroid hormone (PTH) was studied in 6 subjects with normal parathyroid function and one patient with a parathyroid adenoma. In 5 subjects, including the one with the parathyroid adenoma, plasma PTH was measured by radioimmunoassay during a 4-hour infusion of somatostatin (500 mug/h). In 2 subjects, PTH responses to EDTA were compared with those observed during a simultaneous infusion of somatostatin and EDTA. In no instance was ther a discernible effect of the somatostatin infusion on plasma PTH. These results demonstrate that somatostatin does not suppress plasma PTH.
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PMID:Somatostatin does not suppress plasma parathyroid hormone. 82 Jul 4

A number of regulatory peptides were investigated for their ability to elevate plasma cAMP. Pituitary adenylate cyclase activating peptide (PACAP)-27, PACAP-38, helodermin, helospectin I and II, vasoactive intestinal peptide (VIP), glucagon, parathyroid hormone (PTH), calcitonin and calcitonin gene-related peptide were among the peptides that were highly effective in raising plasma cAMP when given intravenously in equimolar doses to conscious mice. PACAP-27 and -38 were more effective than any of the other peptides. PACAP 16-38, secretin, gastrin-17, galanin, somatostatin, cholecystokinin-8s, pancreatic polypeptide, substance P, peptide YY and neuropeptide Y were inactive and also did not interfere with the PACAP-27-evoked rise in plasma cAMP levels. Repeated injections of PACAP-27 every 30 min caused a progressive reduction in the plasma cAMP response (measured 5 min after each injection). Forskolin, an activator of adenylate cyclase, dose-dependently raised the plasma concentration of cAMP and displayed a synergistic effect when given in a low dose concurrently with PTH or PACAP-38. The phosphodiesterase inhibitor rolipram dose-dependently raised the plasma concentration of cAMP. Combined treatment with PACAP-27 and a threshold dose of rolipram resulted in an exaggerated plasma cAMP response. Kidney hilus ligation suppressed the responses to PACAP-38, PTH, helodermin, helospectin, VIP, glucagon and calcitonin. Hepatectomy suppressed the response to glucagon but was without effect on the response to the other peptides. Pancreatectomy and spleenectomy reduced the response to VIP, but was without effect on the response to the other peptides. PACAP-27 stimulated cAMP efflux from the isolated rat tail vein. Hence, it cannot be excluded that blood vessels contribute to the peptide evoked plasma cAMP response in vivo.
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PMID:Neuropeptides of the vasoactive intestinal peptide/helodermin/pituitary adenylate cyclase activating peptide family elevate plasma cAMP in mice: comparison with a range of other regulatory peptides. 133 41

We employed a cyclic AMP-resistant subclone of UMR 106-01 osteoblastic osteosarcoma cells (UMR 4-7) with a regulated, dominant-negative mutation of cyclic AMP-dependent protein kinase (PK-A), to examine the mechanism(s) whereby parathyroid hormone (PTH) regulates growth of these cells. Expression of a transiently transfected CAT reporter gene controlled by the cAMP response element of the rat somatostatin gene ('SST-CAT') was used to monitor PK-A activation in intact cells. Agonist-stimulated SST-CAT expression was specific for agents known to activate adenylate cyclase, required an intact cAMP response element and was specifically blocked following induction of the mutant cAMP-resistant phenotype in UMR 4-7 cells. Inhibition of the proliferation of UMR 106-01 cells by PTH, which is mimicked by forskolin and 8-bromo-cAMP, was blocked completely in mutant cyclic AMP-resistant UMR 4-7 cells. We conclude that control of proliferation in UMR 106-01 cells by PTH involves the cAMP messenger system and requires activation of PK-A.
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PMID:Regulation of gene transcription and proliferation by parathyroid hormone is blocked in mutant osteoblastic cells resistant to cyclic AMP. 135 85

We have established mutant SaOS-2 cell lines that express a cyclic AMP (cAMP)-resistant phenotype to investigate the regulation and functional importance of orthophosphoric-monoester phosphohydrolase alkaline optimum (ALPase) in the action of parathyroid hormone (PTH). Cells were stably transfected with a plasmid that directs the synthesis of a mutant form of the type I regulatory subunit of protein kinase A (PKA) under the control of the metallothionein promotor. There was no significant difference between parental SaOS-2 cells and the mutant lines in the affinity or number of receptors for 125I-Nle8,18Tyr34bPTH1-34NH2, either in the absence or presence of Zn2+. When cAMP-dependent gene transcription was examined using transient transfection with a somatostatin promoter-chloramphenicol acetyl transferase (CAT) reporter plasmid, CAT activity stimulated by human PTH and dibutyryl cAMP (DBcAMP) was inhibited by greater than 90% in the presence of Zn2+ in the mutant cell lines. In contrast, activation by a phorbol ester of a pentameric collagenase promoter/CAT construct containing five tandem copies of the AP-1 response element (5x-TRE-CAT) was unaffected in Zn(2+)-treated mutant cells. The inhibitory actions of PTH and DBcAMP on ALPase release were blunted by up to 80-90% in the mutant cell lines in the presence of Zn2+; there were no significant differences in the magnitude of inhibitory effects between these agonists. We conclude that the inhibitory action of PTH on ALPase release in SaOS-2 cells is mediated via activation of PKA. These cAMP-resistant cell lines will be especially useful in elucidating signal transduction mechanism(s) for PTH in human osteoblastic cells.
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PMID:Protein kinase A-dependent inhibition of alkaline phosphatase release by SaOS-2 human osteoblastic cells: studies in new mutant cell lines that express a cyclic AMP-resistant phenotype. 166 91

We have found vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide (CGRP-2)-, and somatostatin-like immunoreactivities in extracts of sporadic human parathyroid adenomas (n = 18). The content of CGRP-2, substance P, and somatostatin in adenomas correlated directly with that of parathyroid hormone. In addition, concentrations of VIP versus substance P and somatostatin versus CGRP-2 in adenomas were directly correlated. Neuropeptide content of parathyroid hyperplasias differed from that of adenomas. VIP was detected in only one of seven parathyroid hyperplasias, and neurotensin was undetectable (0/7), whereas substance P was present in six of seven cases and GRP in five of seven hyperplasias. In hyperplasias, content of substance P correlated directly with that of gastrin-releasing peptide. Peroxidase immunohistochemistry localized VIP-like immunoreactivity to 20% to 50% of both chief and oxyphilic cells and rare clear cells and capillary endothelium in 11 of 12 adenomas studied. Focal staining was present in glandular epithelium of the rim of adjacent normal parathyroid tissue and in two of three normal parathyroid glands removed with thyroid goiters. This staining was both cytoplasmic and apical membrane. By contrast, in adenomas, neurotensin- and substance P-like positivities were confined to scattered (5% to 10%) oxyphilic cells. Cytoplasmic positivity for parathyroid hormone, noted in 30% to 70% of cells in serial sections, confirmed that these tissues were indeed parathyroid glands.
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PMID:Vasoactive intestinal polypeptide-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide-, and somatostatin-like immunoreactivities in human parathyroid glands. 172 Sep 2

The effects of glucagon on water and electrolyte transport in the kidney were investigated on hormone-deprived rats, i.e. thyroparathyroidectomized diabetes insipidus Brattleboro rats infused with somatostatin. Glucagon consistently inhibited the reabsorption of water and Na+, Cl-, K+ and Ca2+ along the proximal tubule accessible to micropuncture, leaving the reabsorption of inorganic phosphate (Pi) untouched. In the loop, besides its previously described stimulatory effects on Na+, Cl-, K+, Ca2+ and Mg2+ reabsorption, glucagon strongly inhibited Pi reabsorption, very probably in the proximal straight tubule. These effects resulted in a significant phosphaturia and considerable reductions of Mg2+ and Ca2+ excretions. The effects of glucagon at both the whole kidney and the nephron levels are very similar to those previously described for calcitonin. In the absence of an adenylate cyclase system sensitive to glucagon and calcitonin in the rat proximal tubule, and from the analogy of their physiological effects with those elicited by parathyroid hormone, it is suggested that glucagon and calcitonin exert their inhibitory effects on Na and Pi reabsorption in the proximal tubule through another pathway, which could be the phosphoinositide regulatory cascade.
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PMID:Glucagon inhibits water and NaCl transports in the proximal convoluted tubule of the rat kidney. 177 68

We have screened the sequence of the 394 base pairs upstream of the main transcriptional start site of the promoter of the human parathyroid hormone (PTH) gene for well-known protein recognition motifs with the aim to identify potential positive or negative regulatory elements. Within this region we found a potential cAMP-response element (CRE) besides several other putative binding sites for transcription factors. We fused promoter regions that contain this element and extend beyond the transcription start site to an appropriate reporter gene (CAT) and transfected different cell lines with these constructs. Transient expression of the CAT gene from these hybrid genes could be shown to be significantly stimulated by forskolin or isoproterenol thus proving the responsiveness of the whole promoter region towards elevated cAMP levels. DNase I protection studies revealed protein binding around the putative CRE (PTH-CRE) and an adjacent CCAAT element. Gel retardation assays with the PTH-CRE as well as the well-characterized CRE from the rat somatostatin promoter indicated specific binding of the same protein to both elements, although with a slightly reduced affinity of the PTH-CRE. Both of these elements were also able to confer cAMP-responsiveness to a heterologous promoter.
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PMID:The promoter of the human parathyroid hormone gene contains a functional cyclic AMP-response element. 197 34


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