Negative inotropic effects mediated by beta3 adrenoceptors in rat atrial myocytes N. S. Freestone There are currently contradictory reports in the literature concerning the nature of the inotropic effects mediated via the beta3 adrenoceptor in the mammalian myocardium. This study therefore sought to investigate the effect of the beta3 adrenoceptor agonist BRL 37344 on electrically induced Ca ion fluorescence transients in rat atrial myocytes. In addition, under conditions of beta1 and beta2 blockade with propranolol and beta3 adrenoceptor stimulation with BRL 37344, the effect of the propranolol insensitive beta1 adrenoceptor agonist CGP 12177, was also investigated. It was observed that Ca ion fluorescence transients in rat atrial myoctes had a significant diminution in amplitude under conditions of beta3 adrenoceptor stimulation with and without beta1 and beta2 blockade by propranolol. However, when the propranolol insensitive beta1 adrenoceptor agonist CGP 12177 was added in addition to the betablocker and the beta3adrenoceptor ligand a significant increase in the Ca ion fluorescence tranisent amplitude was observed. These results suggest that there are potentially 4 beta adrenoceptor subtypes in rat atrial myocytes. Of these, the beta3 adrenoceptor subtype mediates cardiodepressive effects, as assessed by Ca ion fluorescence transients, whilst the existence of a propranolol resistant and stimulatory beta adrenoceptor is substantiated by the finding of increases in Ca ion fluorescence transient amplitude with CGP 12177 even under conditions of beta1 and beta2 adrenoceptor blockade. atrial myocytes, Ca ion fluorescence, contractility, beta3 adrenoceptors, propranolol insensitive beta1 adrenoceptors Freestone_2007.pdf