Linked Life Data

2886933

Source:http://linkedlifedata.com/resource/pubmed/id/2886933

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pubmed-article:2886933pubmed:dateCreated1987-8-28lld:pubmed
pubmed-article:2886933pubmed:abstractTextIn order to improve our understanding of the ligand specificity of somatostatin (SRIF) receptors in pituitary and brain, and to identify analogs that bind to one type exclusively, we compared several new SRIF analogs for competitive binding to pituitary and cerebral cortex membranes. Binding of [125I-Tyr11]SRIF to hypophysis and brain was of high affinity [KD = 0.76 nM (0.2-1.3) and 0.37 nM(0.1-0.8), mean (95% confidence limits)] and was characteristic of binding to one class of sites in both tissues. Competition by several SRIF analogs for such radioligand binding demonstrated that ligand specificity of adenohypophysial receptors was distinctly different from that of cerebral cortex. Two cyclic octapeptides (sequence; see text) bound to pituitary SRIF receptors with high affinity [Ki = 0.85 nM (0.5-1.2) and 0.35 nM (-0.3-0.9)] and were potent inhibitors of GH secretion from primary cultured pituitary cells [EC50 = 0.009 nM (0-0.02) and 0.017 nM (0.01-0.02), respectively]. However, these selective peptides did not compete (Ki much greater than 1 microM) for radioligand binding to brain. Amidation of the C-terminal end appeared to strikingly alter brain SRIF receptor recognition of the substituted ligand. Indeed, such amidation of the parent peptide, (sequence; see text) resulted in a reduced ability to displace labeled ligand from brain sites [Ki = 165.3 nM (47.6-282.9) to 842.2 nM (603.9-1,081)] but did not affect competition for pituitary receptors. Our results indicate that anterior pituitary SRIF receptors (SRIFa) have ligand specificities which are clearly different from those of their brain counterparts (SRIFb).(ABSTRACT TRUNCATED AT 250 WORDS)lld:pubmed
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pubmed-article:2886933pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:2886933pubmed:year1987lld:pubmed
pubmed-article:2886933pubmed:articleTitleDifferential binding of somatostatin agonists to somatostatin receptors in brain and adenohypophysis.lld:pubmed
pubmed-article:2886933pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:2886933pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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