Differential cholinoceptor subtype-dependent activation of signal transduction pathways in neonatal versus adult rat atria

Biochemical Pharmacology
E BordaL Sterin-Borda

Abstract

In this study, we investigated the expression and distribution of muscarinic cholinergic receptors (mAChRs) and the different signaling pathways associated with mAChR activation in atria isolated from adult and neonatal rats. Carbachol stimulation of mAChRs in both neonatal and adult rat atria led to a negative inotropic response with activation of phosphoinositide hydrolysis, an increase in cyclic GMP levels, and a decrease in cyclic AMP production. However, compared with adult atria, neonatal atria showed hypersensitivity in the contractile effect induced by carbachol. Pharmacological analysis with mAChR antagonists indicated that M1 and M2 mAChR subtypes are important mediators of the response to carbachol in neonatal atria. In contrast, in adult atria the effect of the agonist was coupled only to the M2 mAChR subtype. Moreover, an increased number of total mAChRs was labeled in neonatal atrial membranes compared with those of adults. Although a predominant M2 mAChR population is expressed in atria at both stages of development studied, competition binding parameters calculated for carbachol indicated the presence of high-affinity binding sites, with higher affinity in neonates than in adults. These results suggest that the ...Continue Reading

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Citations

Apr 30, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Jaromir MyslivecekJan Ricny
Dec 1, 1998·European Journal of Pharmacology·A A HislopS G Haworth
Mar 4, 2000·Journal of the Autonomic Nervous System·C P Leirós Santiago BordaE
Jul 13, 1999·International Journal of Cardiology·E BordaL Sterin-Borda
Mar 18, 1999·Clinical Immunology : the Official Journal of the Clinical Immunology Society·C Pérez LeirósE S Borda

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