Orexin receptors couple to Ca2+ channels different from stove-operated Ca2+ channels

We have investigated Ca2+ release and receptor- and store-operated Ca2+ inf luxes in Chinese hamster ovary-ill cells expressing human OX1 orexin recept or. Receptor-operated Ca2+ influx-response to 3 nM orexin-A was not affecte d by Gd3+ or 2-APB (2-aminoethoxydiphenyl berate), but was inhibited by Ni2 +. Store-operated Ca2+ influx was blocked by Ni2+. Gd3+ and 2-APB, whereas the thapsigargin-induced release was unaffected. 2-APB did not block inosit ol-1,4,5-trisphosphate-dependent Ca2+ release in these cells. Thus, low con centrations of orexin-A cause activation of two Ca2+ influxes in the cells: primarily, a receptor-operated Ca2+ influx, and secondarily, a store-deple tion activated Ca2+ influx, which is subsequent to receptor-activated Ca2influx and the therewith-caused IS production. The results show that these two rely on different molecular entities. NeuroReport 12:2017-2020 (C) 2001 Lippincott Williams & Wilkins.