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. T he 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 μM) 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 μM, respectively). Furthermore, AA-induced increase in [Ca2+]i cross-desensitizes with thapsigargin, but AA does not inhibit Ca2+-ATPase activity. These data support the concept that AA concentration-dependently inhibits receptor-mediated NO production at the level of calcium mobilization.
Bibliographical noteFunding Information:
We would like to thank Ms. Marianne Grant for her technical assistance. This work was supported by National Institutes of Health grant NS25743.
- Arachidonic acid
- Calcium signaling
- Muscarinic receptor
- Nitric oxide
- Second messengers
- Signal transduction