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)

In order to investigate the gonadal regulation of pituitary somatostatin receptors (SSTRs)-gene expression, we studied the existence of sexual dimorphism on SSTR1, SSTR2, and SSTR3 mRNA levels in the rat anterior pituitary. The roles of testosterone and other non-androgenic testicular factors were also evaluated. SSTR1, SSTR2 and SSTR3 mRNA content were assessed by in-situ hybridization in male rats lacking the influence of androgenic and/or non-androgenic testicular factors. We found that SSTR1 and SSTR3 mRNA levels in the anterior pituitary exhibited sexual dimorphism. Moreover, our data indicate that SSTR1 mRNA levels are regulated by testosterone, while SSTR3 mRNA content is regulated by non-androgenic testicular factors. In contrast, SSTR2 levels are not influenced by gonadal function.
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PMID:Gonadal regulation of somatostatin receptor 1, 2 and 3 mRNA levels in the rat anterior pituitary. 873 82

Somatostatin and other neuropeptides are known to modulate the proliferative capacity of immune cells. In the present study, we investigated the expression of Somatostatin receptor (SSTR) subtypes on rat thymocytes. RT-PCR analysis of fresh thymocytes showed significant levels of transcripts for the SSTR2 whereas transcripts for the SSTR1 and SSTR3 were not detectable. Interestingly, when the thymocytes were activated with low concentration of Phytohemagglutinin and interleukin 1, the transcript for SSTR1 was markedly increased. Lymphokine induced activation of thymocytes selectively upregulated the SSTR1 since, transcripts for SSTR2 remained the same after activation and SSTR3 was not detectable. PCR amplified fragment of SSTR1 from the activated thymocytes showed identical sequence to the rat brain receptor. The physiological significance of the increase of SSTR1 mRNA in thymocytes after activation remains to be elucidated but it may be possible that these two different subsets of receptors (SSTR1 and SSTR2) are involved in the modulation of thymocyte proliferation and differentiation.
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PMID:Activation of rat thymocytes selectively upregulates the expression of somatostatin receptor subtype-1. 893 24

Somatostatin (SST) exerts direct antiproliferative effects in tumor cells, triggering either growth arrest or apoptosis. The cellular actions of SST are transduced through a family of five distinct somatostatin receptor subtypes (SSTR1-5). Whereas growth inhibition has been reported to follow stimulation of protein tyrosine phosphatase via SSTR2 or inhibition of Ca2+ channels via SSTR5 in heterologous expression systems, the subtype selectivity for signaling apoptosis has not been investigated. The tumor suppressor protein p53 and the protooncogene product c-Myc regulate cell cycle progression (growth factors present) or apoptosis (growth factors absent). The p53-induced G1 arrest requires induction of p21, an inhibitor of cyclin-dependent kinases, whereas apoptosis requires induction of Bax. c-Myc is capable of abrogating p53-induced G1 arrest by interfering with the inhibitory action of p21 on cyclin-dependent kinases. We have, therefore, investigated the regulation of p53, p21, c-Myc, and Bax and cellular apoptosis in relation to cell cycle progression in CHO-K1 cells stably expressing individual human SSTR1-5. We demonstrate that apoptosis is signaled uniquely through human SSTR3 and is associated with dephosphorylation-dependent conformational change in wild-type (wt) p53 as well as induction of Bax. The induction of wt p53 occurs rapidly and precedes the onset of apoptosis. We show that the increase in wt p53 is not associated with the induction of p21 or c-Myc when octreotide-induced apoptosis becomes evident, suggesting that such apoptosis does not require G1 arrest and is not c-Myc dependent. These findings provide the first evidence for hormonal induction of wt p53-associated apoptosis via G protein-coupled receptor in a subtype-selective manner.
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PMID:Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. 896 Dec 77

Distribution of somatostatin receptors (SSTR1-5) was determined in the rat eye. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses revealed that SSTR4 and SSTR2 are major subtypes expressed predominantly in the iris/ciliary body and retina, respectively, and that SSTR1, SSTR3 and SSTR5 are minor subtypes expressed preferentially in the posterior eye segments including the retina. In situ hybridization showed predominant SSTR4 expression in the posterior iris epithelium and ciliary body, suggesting functional roles of somatostatin in the autonomic nervous system in the anterior segments of the eye. The differential expression of SSTR1-5 may be related to distinct roles of somatostatin in the physiology of different ocular tissues.
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PMID:Differential expression of somatostatin receptors in the rat eye: SSTR4 is intensely expressed in the iris/ciliary body. 908 Apr 63

Somatostatin is a general inhibitory hormone that exerts its effects through five functionally distinct receptor subtypes (SSTR1-5). Somatostatin analogues have been shown to be effective in inhibiting intimal hyperplasia after balloon induced vascular injury. However, the exact SSTR subtype responsible for the inhibitory effect of somatostatin on intimal hyperplasia is unknown. The purpose of this study was to define the presence and abundance of SSTR subtypes in a rat iliac balloon injury model of intimal hyperplasia. Transaortic balloon injury of the rat iliac artery was carried out. Rats were sacrificed at 48 h, 1 week, and 1 month postinjury, and perfusion fixed and stained with antibodies against SSTR2, 3, and 5. SSTR2 was identified on the intimal surfaces of normal and injured vessels. SSTR2 immunoreactivity was more prominent at 1 week and 1 month postinjury compared with 48 h postinjury. There was no immunostaining with SSTR3 and SSTR5 antibodies. The results show that SSTR2 is expressed on endothelial cells in normal and injured rat vessels. Its abundance in the injured vessel was increased up to 1 month postinjury.
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PMID:Somatostatin receptor expression in rat iliac arteries after balloon injury. 910 Jan 70

Five somatostatin receptor subtypes (SSTR) have been cloned and characterized in various tissues, including the gastrointestinal tract. This study examined which receptor subtypes mediate the inhibitory actions of somatostatin on gastric acid secretion and gastrin release in conscious dogs. Peptide agonists with relatively high specificity for SSTR1-5 (somatostatin-14), SSTR2 (MK-678), SSTR3 (L-362823), and SSTR5 (L-362855) were infused i.v. after nutrient-stimulated gastric acid secretion and gastrin release with intraduodenal perfusions of 8% peptone and after secretagogue-stimulated acid secretion with gastrin (75 pmol kg-1 h-1) or histamine (20 micrograms kg-1 h-1). At 1000 pmol kg-1 h-1, the SSTR2 agonist inhibited peptone-stimulated acid output to baseline (P < 0.001), whereas the SSTR3 agonist decreased acid output by 58 +/- 6% (P < 0.01): the SSTR5 agonist was without effect. The SSTR2 agonist at 100 pmol kg-1 h-1 also abolished the rise of plasma gastrin. At 50 pmol kg-1 h-1 i.v. infusions of S-14, to simulate circulating S-14 rises after nutrients, decreased peptone-stimulated acid secretion by 58 +/- 8% (P < 0.01), whereas the SSTR2 agonist inhibited gastric acid by 96 +/- 2% (P < 0.001); the SSTR3 agonist was without effect. S-14 or the agonists at 50 pmol kg-1 h-1 did not alter elevations of plasma gastrin. S-14 and the SSTR2 agonist at 50 pmol kg-1 h-1 decreased gastrin-stimulated acid secretion by 42 +/- 8% (P < 0.01) and 78 +/- 4% (P < 0.001), respectively but the SSTR3 and SSTR5 agonists were without effect. In contrast, histamine-stimulated acid secretion was not altered by 1000 pmol kg-1 h-1 S-14 or the agonists. These results in conscious dogs suggest that the inhibitory actions of circulating S-14 on nutrient and gastrin-stimulated acid secretion include activation of the SSTR-2 subtype. Regulation of gastrin release by S-14 may also occur via SSTR-2, but not through an endocrine mechanism. Factors in addition to gastrin and histamine modulate intestinal protein-stimulated acid secretion yet include peripheral S-14 inhibition via SSTR2 activation.
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PMID:Characterization of somatostatin receptor subtypes mediating inhibition of nutrient-stimulated gastric acid and gastrin in dogs. 910 Feb 87

SSTR3, a somatostatin (SST) receptor, is an adenylyl cyclase (AC)-inhibiting receptor. To assign the G-protein alpha-subunit (G alpha) linked to this receptor, we created a novel reporter system which utilizes the well-established facts that the C-terminal 5 residues of G alpha are the receptor contact site and G alpha(s) stimulates all subtypes of AC. We constructed chimeric G alpha(s) the C-terminal 5 residues of which were replaced with the corresponding C-terminus of each known G alpha, and examined which chimera confers SSTR3-induced activation of AC. Cellular transfection of SSTR3 and measurement of SST-dependent AC activity through co-transfected chimeric G alpha(s) revealed that SSTR3 recognizes the C-termini of G alpha(i1/2) but not of G alpha(o) or G alpha(z), and those of G alpha(14) and G alpha(16), but not of G alpha(q) or G alpha(11). As predicted by the chimeric G alpha(s), SST-bound SSTR3 stimulated polyphosphoinositide turnover only when G alpha(16) or G alpha(14) was co-transfected. We conclude that the chimeric G alpha(s) system provides a new approach towards the assignment of G-proteins linked to a given receptor.
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PMID:A novel system that reports the G-proteins linked to a given receptor: a study of type 3 somatostatin receptor. 910 10

Somatostatin significantly suppressed cell growth of the mouse insulinoma-derived cell line MIN6. MIN6 cells exhibited high-affinity binding of somatostatin with 50% inhibitory concentration value of 0.9 nM. RNA blot analysis revealed that MIN6 cells expressed only SSTR3 among the five somatostatin receptors so far identified. Treatment of MIN6 cells with somatostatin significantly reduced the serum-induced c-fos expression levels. On the other hand, somatostatin (100 nM) treatment of MIN6 cells cultured in medium containing 10% serum transiently increased c-fos expression levels to 282 +/- 4.7% and then significantly decreased them to 27 +/- 7.6% of the levels before treatment. Mitogen-activated protein (MAP) kinase activity transiently increased to 656 +/- 91.2% and decreased thereafter to 39 +/- 13.3% of the activity before the addition of somatostatin (100 nM) into the medium. In addition, the stimulatory effect of somatostatin on c-fos expression and MAP kinase activity (early effect) was not altered by pertussis toxin (PTX), whereas the suppressive effect of somatostatin on c-fos expression and MAP kinase activity (late effect) was mitigated by PTX. These findings suggest that an inhibition of c-fos expression mediated by cross talk between PTX-sensitive G protein signaling and receptor tyrosine kinase signaling is one of the mechanisms by which somatostatin inhibits cell growth in MIN6 cells.
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PMID:Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin. 917 74

Somatostatin (SRIH) analogs can suppress the proliferation of human differentiated thyroid carcinoma cell lines that express SRIH receptors (SSTRs) demonstrated by radioligand binding analysis. Five distinct human SSTR subtypes (hSSTR1-5) that bind native SRIH exhibit diverse affinities to a wide range of SRIH analogs. Reverse transcriptase-PCR amplification of ribonucleic acids (RNAs) obtained from normal thyroid tissues and nine human thyroid carcinoma cell lines, grown as monolayer cultures and xenograft tumors in nude mice, were used to discriminate expression of SSTR subtype messenger RNAs (mRNAs). The cell lines were derived from a follicular adenoma (KAK-1), two follicular carcinomas (MRO-87 and WRO-82), two papillary carcinomas (NPA87 and KAT-10), and four anaplastic thyroid carcinomas (DRO-90, ARO-81, KAT-4, and KAT-18). Most thyroid cancer cell line monolayers and xenografts expressed SSTR3 and SSTR5 mRNAs. SSTR1 expression was more varied between monolayers and xenografts, whereas SSTR2 mRNA was only faintly detectable at the most extreme resolution. SSTR4 mRNA was faintly positive in only one anaplastic carcinoma xenograft. Normal thyroid also expressed SSTR3 and SSTR5 mRNAs, with only faint expression of SSTR1 and SSTR2 mRNAs (in one of five and three of five samples, respectively). SSTR mRNA expression was dependent upon in vitro culture conditions, as xenograft SSTR mRNA expression tended to decrease compared to that in each respective monolayer culture. Characterization of SSTR subtype expression in human thyroid carcinomas may permit targeting of specific SRIH analogs to inhibit proliferation of differentiated and anaplastic thyroid carcinomas in patients.
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PMID:Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines. 917 96

Somatostatin and its analogues are now of current use in the management of endocrine gastroentero-pancreatic (GEP) tumours for the purpose of inhibiting hormone hypersecretion, carrying scintigraphy imaging and attempting to slow down tumour growth. Recent molecular studies have revealed the existence of up to five membrane somatostatin receptor subtypes termed SSTR1-5. However, whether or not scintigraphy imaging and tumour characteristics are correlated with specific subtype(s) remains unclear. SSTR1-5 messenger RNA (mRNA) transcripts were investigated in 38 endocrine GEP tumours (32 islet cell tumours, six carcinoid) using reverse transcriptase polymerase chain reaction (RT-PCR), and their distribution was analysed with respect to tumour characteristics and scintigraphy imaging. SSTR2, SSTR5 and SSTR4 were detected in most cases of endocrine GEP tumours (92%, 84%, and 82% respectively), but SSTR1 and SSTR3 were less frequently observed (66% and 50% respectively). No clear-cut correlation was found between tumour characteristics and subtype mRNA distribution. Moreover, no differences in mRNA subtype distribution were found between the 17 tumours detected by scintigraphy and the four tumours not detected by this method. Somatostatin receptor mRNA subtypes are widely expressed in endocrine GEP tumours, but their distribution is not correlated with tumour characteristics or scintigraphy positivity.
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PMID:Somatostatin receptor subtype gene expression in human endocrine gastroentero-pancreatic tumours. 927 25


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