title: Nonpeptidyl somatostatin agonists demonstrate that sst2 and sst5 inhibit stimulated growth hormone secretion from rat anterior pituitary cells.
abstract: Somatostatin (SST) regulates growth hormone (GH) secretion from pituitary somatotrophs by interacting with members of the SST family of G-protein-coupled receptors (sst1-5). We have used potent, nonpeptidyl SST agonists with sst2 and sst5 selectivity to determine whether these receptor subtypes are involved in regulating growth hormone releasing hormone (GHRH) stimulated secretion. GHRH stimulated GH release from pituitary cells in a dose-dependent manner, and this secretion was inhibited by Tyr(11)-SST-14, a nonselective SST analog. A sst2 selective agonist, L-779,976, potently inhibited GHRH-stimulated GH release. In addition, L-817, 818, a potent sst5 receptor selective agonist, also inhibited GH secretion, but was approximately 10-fold less potent (P < 0.01, ANOVA) in inhibiting GH release than either Tyr(11)-SST-14 or L-779, 976. These results show that both sst2 and sst5 receptor subtypes regulate GHRH-stimulated GH release from rat pituitary cells.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey, 07065, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Parmar
authors.forename: W W
authors.initials: WW
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Dashkevicz
authors.forename: E C
authors.initials: EC
authors.lastname: Hayes
authors.forename: S P
authors.initials: SP
authors.lastname: Rohrer
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Schaeffer
authors.forename: A D
authors.initials: AD
authors.lastname: Blake
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D007211:Indoles; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000819:agonists*; D013004:Somatostatin / Q000819:agonists* / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000577:Amides; D007211:Indoles; C121854:L 779976; D017481:Receptors, Somatostatin; C121799:somatostatin 14, Tyr(11)-; D013004:Somatostatin; C094573:somatostatin receptor 5; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C093733:somatostatin receptor 2