Subtypes of somatostatin receptors are expressed in the anterior pituitary cell line GH3.
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.
Raynor
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K
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia.
Reisine
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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
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