Orexin receptors couple to Ca2+ channels different from store-operated Ca2+ channels.
We have investigated Ca2+ release and receptor- and store-operated Ca2+ influxes in Chinese hamster ovary-K1 cells expressing human OX1 orexin receptor. Receptor-operated Ca2+ influx-response to 3 nM orexin-A was not affected by Gd3+ or 2-APB (2-aminoethoxydiphenyl borate), 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 inositol-1,4,5- trisphosphate-dependent Ca2+ release in these cells. Thus, low concentrations of orexin-A cause activation of two Ca2+ influxes in the cells: primarily, a receptor-operated Ca2+ influx, and secondarily, a store-depletion activated Ca2+ influx, which is subsequent to receptor-activated Ca2+ influx and the therewith-caused IP3 production. The results show that these two rely on different molecular entities.
Kukkonen
J P
JP
Department of Physiology, Division of Cell Physiology, Uppsala University, BMC, P.O. Box 572, SE-75123 Uppsala, Sweden.
Akerman
K E
KE
D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D019284:Thapsigargin