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Differential Involvement of the Arachidonic Acid Cascade on the α 1 ‐Adrenergic Potentiation of Vasoactive Intestinal Peptide‐Versus β‐Adrenergic‐Stimulated Cyclic AMP and Cyclic GMP Accumulation in Rat Pinealocytes
Author(s) -
Chik Constance L.,
Young Indranie,
Ho Anthony K.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb06348.x
Subject(s) - nordihydroguaiaretic acid , pinealocyte , medicine , arachidonic acid , endocrinology , vasoactive intestinal peptide , long term potentiation , adrenergic , adrenergic agent , pde10a , biology , second messenger system , cyclic nucleotide , phosphodiesterase 3 , chemistry , phosphodiesterase , receptor , pineal gland , biochemistry , melatonin , neuropeptide , nucleotide , enzyme , gene
: In the rat pineal gland, α 1 ‐adrenergic agonists, which stimulate arachidonic add release, also potentiate vasoactive intestinal peptide.(VIP)‐or β‐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 α 1 ‐adrenergic potentiation of VIP‐or β‐adrenergic‐stimulated cAMP and cGMP responses. Whereas nordihydroguaiaretic acid was effective in suppressing both the α 1 ‐adrenergic potentiation of VIP‐or β‐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—A 2 , I 2 , E 2 , and F 2α —and leukotrienes—B 4 , C 4 , and D 4 . Of the seven compounds tested, prostaglandins E 2 and F 2α stimulated basal cAMP but not cGMP accumulation. The prostaglandin E 2 ‐and F 2α ‐stimulated cAMP responses were additive to those stimulated by VIP or β‐adrenergic receptors. The other five compounds had no effects on basal or VIP‐or β‐adrenergic‐stimulated cAMPor cGMP accumulation. Taken together, these findings indicate that the arachidonic acid cascade is likely involved in the α 1 ‐adrenergic potentiation of VIP‐or β‐adrenergic‐stimulated cAMP and cGMP accumulation. However, the specific arachidonic acid metabolite involved in the potentiation mechanisms of VIP‐versus β‐adrenergic‐stimulated cyclic nucleotide responses may be different.