Alpha 1-adrenoceptor subtype involved in the positive and negative inotropic responses to phenylephrine in rat papillary muscle

1. In rat papillary muscle, stimulation of alpha 1-adrenoceptors results in a biphasic inotropic response: a transient negative inotropic phase and a subsequent sustained positive inotropic phase. This study was designed to determine whether the positive and negative inotropic effects in this tissue are mediated by different alpha 1-adrenoceptor subtypes. 2. After treatment with the tumor-promoting compound, phorbol 12, 13-dibutyrate, phenylephrine (in the presence of propranolol) produced only a positive inotropic effect. The selective alpha 1A-adrenoceptor antagonist, WB4101, significantly inhibited the positive inotropic effect. In contrast, inactivation of alpha 1B-adrenoceptors with chloroethylclonidine (CEC) did not alter the positive effect. 3. In the presence of the Ca2+ channel antagonist, nifedipine, phenylephrine induced only a sustained negative inotropic effect. The negative inotropic effect was significantly attenuated by WB4101, but was not affected by CEC. 4. We conclude that both the positive and negative inotropic responses of rat papillary muscle to phenylephrine are mediated exclusively by the WB4101-sensitive but CEC-resistant alpha 1-adrenoceptor subtype. The alpha 1-adrenoceptor subtype with such a property may correspond to the alpha 1A-subtype.