title: Desensitization of cholecystokininB receptors in GH3 cells.
abstract: Desensitization of the cholecystokinin (CCK) octapeptide (CCK-8)-induced rise in intracellular free calcium concentration ([Ca2+]i) was characterized in GH3 cells, a pituitary tumor cell line, which are known to possess CCKB receptor subtype. The CCK-8-induced [Ca2+]i transient was reduced following the initial application of CCK-8. A similar desensitization of the CCK-8-induced response was observed following the first application of thyrotropin-releasing hormone (TRH). By contrast, the TRH-induced response was not desensitized by the preceding application of CCK-8. Desensitization of the CCK-8-induced [Ca2+]i transient was associated with diminished inositol 1,4,5-trisphosphate formation. The recovery of desensitization of the CCK-8-induced response was delayed by a phosphoserine/phosphothreonine phosphatase inhibitor, calyculin A (100 nM). The responsiveness to CCK-8 was also reduced by phorbol 12,13-dibutyrate (PDBu), and this effect of PDBu was completely abolished by preincubation with staurosporine. Staurosporine significantly attenuated the desensitization caused by preincubation with CCK-8, but this effect was too small to attribute the desensitization to the protein kinase C transduction pathway alone. It is likely that desensitization of CCK receptors involves multiple transduction pathways.
authors.affiliation: Division of Pharmacology, Kanzakigawa Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shinohara
authors.forename: K
authors.initials: K
authors.lastname: Kawasaki
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004361:Drug Tolerance; D004789:Enzyme Activation / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010911:Pituitary Neoplasms; D011493:Protein Kinase C / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology*; D019311:Staurosporine; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D008387:Marine Toxins; D010080:Oxazoles; D011949:Receptors, Cholecystokinin; D015240:Phorbol 12,13-Dibutyrate; D013973:Thyrotropin-Releasing Hormone; C059041:calyculin A; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; C045903:phosphothreonine phosphatase; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase; D019311:Staurosporine; D012844:Sincalide; D002118:Calcium