Pertussis toxin-sensitive and -insensitive mechanisms of α 1-adrenoceptor-mediated inotropic responses in rat heart

Abstract

In rat left ventricular papillary muscle, phenylephrine, an α1-adrenoceptor agonist, induced a triphasic inotropic response; an initial transient, small, positive inotropic effect followed by a transient chloroethylclonidine-sensitive negative inotropic effect and a sustained 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB4101)-sensitive positive inotropic effect. Treatment with pertussis toxin for 2 days significantly inhibited only the transient negative inotropic effect without changing the sustained positive inotropic effect. This treatment also prevented the acetylcholine (1 μM)-induced negative inotropic effect. Further, phenylephrine-induced transient negative inotropic effect was attenuated in the presence of ouabain. These results suggest that pertussis toxin-sensitive or-insensitive G-protein may be responsible for α1-adrenoceptor subtype-mediated negative inotropic effect or positive inotropic effect, respectively, in which the transient negative inotropic effect was produced via the stimulation of Na +, K + pump, presumably through pertussis toxin-sensitive G-protein-dependent pathway.