Effects of procaine on pharmaco-mechanical coupling mechanisms activated by acetylcholine in smooth muscle cells of porcine coronary artery.
The action of procaine on pharmaco-mechanical coupling activated by application of acetylcholine (ACh) was investigated using collagenase-treated dispersed intact and skinned smooth muscle cells and intact muscle tissues of the porcine coronary artery. ACh reduced stored 45Ca2+, and this action was prevented by procaine in intact dispersed cells. The maximum reduction in the level of stored 45Ca induced by caffeine (25 mM) or inositol 1,4,5-trisphosphate (InsP3; 3 microM) was also prevented by procaine in the skinned muscle cells in the presence or absence of ATP. However, inhibitions of the latter required higher concentrations of procaine than the former. Release by 10 microM ACh of Ca2+ from its store site in the presence or absence of extracellular Ca2+ was also inhibited by procaine and was detected using the quin2 fluorescence method. In these smooth muscle tissues, ACh (above 10 nM) reduced the amount of phosphatidylinositol 4,5-bisphosphate (PI-P2) and dose dependently increased the amount of phosphatidic acid. Procaine inhibited the hydrolysis of PI-P2 activated by ACh, thus reducing the amount of InsP3 and the release of Ca2+ from the store site. It is concluded that procaine has multiple actions on the porcine coronary artery, and one of the actions related with pharmacomechanical coupling appears through inhibition of hydrolysis of PI-P2 induced by ACh.
D000109:Acetylcholine / Q000494:pharmacology*; D000634:Aminoquinolines; D000818:Animals; D001158:Arteries; D001696:Biomechanical Phenomena; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects*; D005453:Fluorescence; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology*; D013552:Swine
D000634:Aminoquinolines; D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D002110:Caffeine; D011343:Procaine; D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine; C035739:Quin2; D002118:Calcium