Differential involvement of the arachidonic acid cascade on the alpha 1-adrenergic potentiation of vasoactive intestinal peptide- versus beta-adrenergic-stimulated cyclic AMP and cyclic GMP accumulation in rat pinealocytes.
In the rat pineal gland, alpha 1-adrenergic agonists, which stimulate arachidonic acid release, also potentiate vasoactive intestinal peptide (VIP)- or beta-adrenergic-stimulated cyclic AMP (cAMP) and cyclic GMP (cGMP) accumulation. In this study, the possible involvement of the arachidonic acid pathway in the potentiation mechanism was examined in dispersed rat pinealocytes using two inhibitors of the arachidonic acid cascade, indomethacin and nordihydroguaiaretic acid. These two inhibitors appeared to have differential effects on the alpha 1-adrenergic potentiation of VIP- or beta-adrenergic-stimulated cAMP and cGMP responses. Whereas nordihydroguaiaretic acid was effective in suppressing both the alpha 1-adrenergic potentiation of VIP- or beta-adrenergic-stimulated cAMP and cGMP responses, indomethacin inhibited selectively the VIP-mediated cAMP and cGMP responses. The role of arachidonic acid metabolites was further determined using several prostaglandins--A2, I2, E2, and F2 alpha--and leukotrienes--B4, C4, and D4. Of the seven compounds tested, prostaglandins E2 and F2 alpha stimulated basal cAMP but not cGMP accumulation. The prostaglandin E2- and F2 alpha-stimulated cAMP responses were additive to those stimulated by VIP or beta-adrenergic receptors. The other five compounds had no effects on basal or VIP- or beta-adrenergic-stimulated cAMP or cGMP accumulation. Taken together, these findings indicate that the arachidonic acid cascade is likely involved in the alpha 1-adrenergic potentiation of VIP- or beta-adrenergic-stimulated cAMP and cGMP accumulation. However, the specific arachidonic acid metabolite involved in the potentiation mechanisms of VIP- versus beta-adrenergic-stimulated cyclic nucleotide responses may be different.
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Department of Medicine, University of Alberta, Edmonton, Canada.
Young
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D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D009637:Masoprocol / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D001095:Arachidonic Acids; D011453:Prostaglandins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D014660:Vasoactive Intestinal Peptide; D009637:Masoprocol; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D007213:Indomethacin