title: Ca(2+) influx through nonselective cation channels plays an essential role in noradrenaline-induced arachidonic acid release in Chinese hamster ovary cells expressing alpha(1A)-, alpha(1B)-, or alpha(1D)-adrenergic receptors.
abstract: We constructed Chinese hamster ovary (CHO) cells stably expressing alpha(1A)-, alpha(1B)-, or alpha(1D)-adrenergic receptors (CHO-alpha(1A), CHO-alpha(1B), or CHO-alpha(1D), respectively) and compared the Ca(2+) channels activated by noradrenaline (NA) in these cells using whole-cell recordings and monitoring of the intracellular free Ca(2+) concentration ([Ca(2+)](i)). We also investigated the involvement of Ca(2+) channels in the NA-induced arachidonic acid release. In all three cell types, NA at concentrations > or =10 nM induced a sustained increase in [Ca(2+)](i) attributable to extracellular Ca(2+) influx in [Ca(2+)](i) monitoring and an inward current in whole-cell recording. The current-voltage relationships were linear, and their reversal potentials were close to 0 mV. The reversal potential of the currents was not affected by a change in the concentration of Cl(-) in the bath solution. Moreover, a current could be induced in a bath solution containing only Ca(2+) as the movable cation. LOE 908, a receptor-operated Ca(2+) channel blocker, inhibited the sustained increase in [Ca(2+)](i) and inward currents in a concentration-dependent manner, and complete inhibition was observed at concentrations > or = 3 microM. NA induced arachidonic acid release in all three cell types. This release was entirely dependent on extracellular Ca(2+) influx. Moreover, LOE 908 at concentrations > or = 3 microM blocked the NA-induced increase in arachidonic acid release. These results indicate that 1) NA activates LOE 908-sensitive Ca(2+)-permeable nonselective cation channels (NSCCs) in CHO-alpha(1A), CHO-alpha(1B), and CHO-alpha(1D), and 2) the Ca(2+) influx through NSCCs may play an important role in the NA-induced enhancement of arachidonic acid release in these cells.
authors.affiliation: Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan. kawanabe@kuhp.kyoto-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kawanabe
authors.forename: N
authors.initials: N
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: S
authors.initials: S
authors.lastname: Miwa
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D006224:Cricetinae; D004347:Drug Interactions; D004594:Electrophysiology; D007295:Inositol Phosphates / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism* / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism
chemical_list: D000081:Acetamides; D000316:Adrenergic alpha-Agonists; D002412:Cations; D007295:Inositol Phosphates; D007473:Ion Channels; D007546:Isoquinolines; D018340:Receptors, Adrenergic, alpha-1; C081356:LOE 908; D016718:Arachidonic Acid; D002118:Calcium; D009638:Norepinephrine