PHARMACOLOGICAL EVIDENCE FOR THE EXISTENCE OF DIFFERENT SUBTYPES OF MUSCARINIC ACETYLCHOLINE-RECEPTORS FOR PHOSPHOINOSITIDE HYDROLYSIS IN NEONATAL VERSUS ADULT-RAT ATRIA

The negative inotropic effect of carbachol, as well as phosphoinositid e hydrolysis, was measured in atria from neonatal and adult rats. Carb achol increased phosphoinositide hydrolysis and decreased dF/dt of bot h neonatal and adult atria; however, the neonatal atria showed hyperea ctivity to carbachol as compared with adult atria. Inhibition of phosp holipase C reduced the supersensitivity to carbachol upon contractilit y in neonatal atria producing values similar to those of the adult atr ia, suggesting that muscarinic acetylcholine receptor (mAchR) stimulat ion is secondary to receptor-mediated hydrolysis of phosphoinositides. Pharmacological analysis with mAchR antagonists tends to support the idea that mi and m2 subtypes are the most important mediators of the r esponse to carbachol in neonatal atria. In adult atria, the effect of carbachol is coupled only to mAchR m2 subtypes.