title: Effector coupling of somatostatin receptor subtypes on human endocrine tumors.
abstract: Effector coupling of somatostatin receptor subtypes sst1 and sst2 was examined in a reconstituted system. Forskolin-stimulated cyclic adenosine monophosphate (cAMP) formation was inhibited 66% by somatostatin (SRIF-14) in CHO cells expressing somatostatin receptor 1(sst1) (CHO-SR1), but not sst2, in a dose-dependent manner with an ED50 of 1 x 10(-9) mol/L SRIF-14. The inhibition was blocked by pertussis toxin (PTX), indicating that sst1 is coupled to adenylyl cyclase via PTX-sensitive Gi protein. In CHO cells, Gi alpha 2 and Gi alpha 3 mRNAs were detected. In adenylyl cyclase assays, 1 mumol/L SRIF-14 caused a 16% inhibition of forskolin-stimulated adenyly cyclase activity. Preincubation with Gi alpha 3, but not Gi alpha 1/Gi alpha 2, antiserum blocked this inhibition. By contrast, sst2 is coupled to adenylyl cyclase via Gi alpha 1. In cells expressing sst2 with Gi alpha 1(CHO-SR2G1), SRIF-14 significantly inhibited forskolin-stimulated cAMP formation by 53% and with an ED50 at 4 x 10(-9)mmol/L SRIF-14, which was completely blocked by PTX; ED50 values for sst1 and sst2 agree with the IC50 values in binding assays. In CHO-SR1, the rank of potency of agonists affecting adenyl cyclase was SRIF-14 = SRIF-28 > RC 160 > SMS 201-995. In CHO-SR2G1, the rank was RC-160 > SRIF-14 = SRIF-28 > SMS 201-995.
authors.affiliation: Department of Metabolism and Clinical Nutrition, Kyoto University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kubota
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Kagimoto
authors.forename: S
authors.initials: S
authors.lastname: Seino
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
mesh_terms: D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004701:Endocrine Gland Neoplasms / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D037342:Pertussis Toxin; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D013004:Somatostatin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases