Arachidonic acid inhibition of muscarinic receptor-mediated nitric oxide production occurs at the level of calcium mobilization in Chinese hamster ovary cells.
Strong evidence supports that nitric oxide (NO) alters cell signaling pathways involving arachidonic acid (AA). Little is known, however, about the reciprocal modulation of nitrergic pathways by AA. The effects of exogenous AA on signal transduction of M1 muscarinic acetylcholine receptors were investigated in a model system of stably transfected Chinese hamster ovary cells. AA concentration-dependently inhibited the effects of carbachol in producing NO (IC50 = 191 microM) but did not alter inositol phosphate production or M1 receptor binding. AA inhibited both carbachol-induced transient and sustained increase in intracellular calcium concentration ([Ca2+]i; IC50 = 11 and 12 microM, respectively). Furthermore, AA-induced increase in [Ca2+]i cross-desensitizes with thapsigargin, but AA does not inhibit Ca(2+)-ATPase activity. These data support the concept that AA concentration-dependently inhibits receptor-mediated NO production at the level of calcium mobilization.
Division of Neuroscience Research in Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA.
David R
DR
Linden
Esam E
EE
el-Fakahany
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D016718:Arachidonic Acid; D009569:Nitric Oxide; D002217:Carbachol; D002118:Calcium