Homologous and heterologous desensitisation of somatostatin-induced increases in intracellular Ca2+ and inositol 1,4,5-trisphosphate in CHO-K1 cells expressing human recombinant somatostatin sst5 receptors

The mechanisms responsible for somatostatin (SRIF)-induced increases in intracellular Ca2+ concentration ([Ca2+](i)) and subsequent desensitisation were studied in CHO-K1 cells expressing human sst, receptors (CHOsst(5) cells). To study the nature of the desensitisation, interactions with uridine triphosphate (UTP) were examined. SRIF (pEC(50) 7.10) and UTP (pEC(50) 5.14) caused concentration-dependent increases in [Ca2+](i) but the SRIF maximum was about 40% of that to UTP. SRIF-, but not UTP-, induced increases in [Ca2+](i) were transient and abolished by pertussis toxin. SRIF and UTP caused sustained increases in Ins(1,4,5)P-3 but the SRIF maximum was about 30% of that to UTP. Removal of [Ca2+](e) attenuated the SRIF-induced peak rise in [Ca2+](i) but had no effect on the peak increases in Ins(1,4,5)P-3. UTP-induced increases in [Ca2+](i) and Ins(1,4,5)P-3 were attenuated in the absence of [Ca2+](e). Following pre-exposure to SRIF(1 mu M) or UTP (100 mu M) for 5 min, subsequent SRIF responses were desensitised. Similar results were obtained in the absence of [Ca2+](e). Pre-exposure to SRIF had no effect on subsequent responses to UTP but in the absence of [Ca2+](e), responses to UTP were attenuated. The results suggest that SRIF but not UTP-induced increases in [Ca2+](i) in CHOsst(5) cells are mediated by pertussis toxin sensitive G proteins and are caused by an entry of extracellular Ca2+ and release from an Ins(1,4,5)P-3 sensitive Ca2+ store. Homologous or heterologous desensitisation of agonist-induced increases in [Ca2+](i) could be demonstrated in the presence or absence of extracellular Ca2+ respectively, and the latter appeared to involve depletion of a common intracellular Ca2+ store. (C) 1997 Elsevier Science B.V.