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

In rat left ventricular papillary muscle, phenylephrine, an alpha1-adrenoce ptor agonist, induced a triphasic inotropic response; an initial transient, small, positive inotropic effect followed by a transient chloroethylclonid ine-sensitive negative inotropic effect and a sustained 2-(2,6-dimethoxyphe noxyethyl)aminomethyl-1,4-benzodioxane (WD4101)-sensitive positive inotropi c effect. Treatment with pertussis toxin for 2 days significantly inhibited only the transient negative inotropic effect without changing the sustaine d positive inotropic effect. This treatment also prevented the acetylcholin e (1 muM)-induced negative inotropic effect. Further, phenylephrine-induced transient negative inotropic effect was attenuated in the presence of ouab ain. These results suggest that pertussis toxin-sensitive or-insensitive G- protein may be responsible for alpha1-adrenoceptor subtype-mediated negativ e 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-dependen t pathway. (C) 2001 Elsevier Science B.V. All rights reserved.