Inhibitory effects of cyclic AMP-elevating agents on norepinephrine-induced phosphatidylinositide hydrolysis and contraction in rat aorta.
1. Exposure of rat aorta to forskolin, dibutyryl cyclic AMP, rolipram or isobutylmethylxanthine partially prevented the increased inositol monophosphate accumulation due to norepinephrine, while the contractile responses to norepinephrine were almost completely inhibited. 2. Inhibition of the increased phosphatidylinositide synthesis due to norepinephrine could not account for the decreased inositol monophosphate accumulation. 3. Although the increased inositol monophosphate accumulation due to norepinephrine was partially inhibited by the cyclooxygenase inhibitor, indomethacin, the inhibitory effects of the cyclic AMP-elevating agents were still observed in the presence of indomethacin. 4. Inhibition of agonist-induced phosphatidylinositide hydrolysis may contribute, at least in part, to the vasodilatory effects of the cyclic AMP-elevating agents.
Rapoport
R M
RM
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020889:Rolipram
D001095:Arachidonic Acids; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D016718:Arachidonic Acid; D003994:Bucladesine; D000242:Cyclic AMP; D020889:Rolipram; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine; D007213:Indomethacin