Muscarinic receptor-mediated prostacyclin and cGMP synthesis in cultured vascular cells.
The purpose of the present study was to determine the subtype of muscarinic receptor involved in the action of cholinergic stimuli on synthesis of prostacyclin, measured as immunoreactive 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and cGMP in bovine aortic endothelial and rabbit vascular smooth muscle cells. Acetylcholine and arecaidine propargyl ester, a selective M2 agonist, produced a dose-dependent increase in 6-keto-PGF1 alpha output and cGMP formation in confluent endothelial cells but not in confluent vascular smooth muscle cells. McN-A-343, a selective M1 agonist, failed to alter basal 6-keto-PGF1 alpha or cGMP synthesis. Acetylcholine- and arecaidine propargyl ester-induced 6-keto-PGF1 alpha synthesis and cGMP formation in endothelial cells were attenuated by atropine, AF-DX 116 (M2 antagonist), and hexahydrosiladifenidol (M3 antagonist) but not by pirenzepine (M1 antagonist). The cyclooxygenase inhibitor indomethacin abolished 6-keto-PGF1 alpha synthesis but not the increase in cGMP formation elicited by the cholinergic stimuli. Our data suggest that the effect of cholinergic stimuli to enhance prostacyclin and cGMP synthesis is mediated via activation of M2 and M3 receptors located on endothelial cells and that the increase in cGMP production is independent of prostaglandins.
Department of Pharmacology, University of Tennessee, Memphis 38163.
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Jaiswal
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Jaiswal
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KU
Malik
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001115:Arecoline / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology*
D006584:Hexamethonium Compounds; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C015000:arecaidine esters; D000001:Calcimycin; D018738:Hexamethonium; D001115:Arecoline; D015121:6-Ketoprostaglandin F1 alpha; D011433:Propranolol; D011464:Epoprostenol; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine; D010646:Phentolamine