title: Subtypes of somatostatin receptors are expressed in the anterior pituitary cell line GH3.
abstract: GH3 cells express receptors for the neuropeptide somatostatin (SRIF). In the present study, we have identified and characterized SRIF1 and SRIF2 receptors in GH3 cells using the radioligands [125I]MK 678 and [125I]CGP 23996. [125I]MK 678 binding to SRIF1 receptors was saturable and of high affinity and was potently inhibited by SRIF analogs with a rank order of potency of MK 678 > SRIF > SRIF 28 > CGP 23996. [125I]CGP 23996 binding to SRIF2 receptors was also saturable and of high affinity, and was potently inhibited by SRIF analogs with a rank order of potency of SRIF 28 > SRIF > CGP 23996, but was not inhibited by MK 678. Agonist pretreatment of GH3 cells differentially regulated SRIF1 and SRIF2 receptors. [125I]MK 678 binding to SRIF1 receptors was readily diminished after pre-exposure of GH3 cells to SRIF or MK 678. [125I]CGP 23996 binding to SRIF2 receptors was unaffected by pretreatment with MK 678 and was only partially affected by pretreatment with SRIF. [125I]MK 678 binding to SRIF1 receptors was abolished in the presence of the nonhydrolyzable GTP analog guanosine-5'-O-(3-thio)triphosphate, but [125I]CGP 23996 binding to SRIF2 receptors was unaffected. The SRIF1 receptor mediates inhibition of adenylyl cyclase activity, as SRIF and MK 678 inhibited forskolin-stimulated cyclic AMP accumulation in these cells to the same extent. GH3 cells are a unique model system for investigations of the pharmacological, biochemical and functional properties of these two receptor subclasses.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: K
authors.initials: K
authors.lastname: Raynor
authors.forename: T
authors.initials: T
authors.lastname: Reisine
mesh_terms: D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure*; D051381:Rats; D017481:Receptors, Somatostatin / Q000145:classification* / Q000187:drug effects / Q000502:physiology; D012680:Sensitivity and Specificity; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013268:Stimulation, Chemical; D013696:Temperature; D013997:Time Factors
chemical_list: D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D005576:Colforsin; D013004:Somatostatin; C040968:seglitide; C038136:CGP 23996; D000242:Cyclic AMP; D019204:GTP-Binding Proteins