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 resu lts in a biphasic inotropic response: a transient negative inotropic p hase and a subsequent sustained positive inotropic phase. This study w as designed to determine whether the positive and negative inotropic e ffects in this tissue are mediated by different alpha(1)-adrenoceptor subtypes. 2. After treatment with the tumor-promoting compound, phorbo l 12,13-dibutyrate, phenylephrine (in the presence of propranolol) pro duced only a positive inotropic effect. The selective alpha(1A)-adreno ceptor antagonist, WB4101, significantly inhibited the positive inotro pic effect. In contrast, inactivation of alpha(1B)-adrenoceptors with chloroethylclonidine (CEC) did not alter the positive effect. 3. In th e presence of the Ca2+ channel antagonist, nifedipine, phenylephrine i nduced only a sustained negative inotropic effect. The negative inotro pic effect was significantly attenuated by WB4101, but was not affecte d by CEC. 4. We conclude that both the positive and negative inotropic responses of rat papillary muscle to phenylephrine are mediated exclu sively by the WB4101-sensitive but CEC-resistant alpha(1)-adrenoceptor subtype. The alpha(1)-adrenoceptor subtype with such a property may c orrespond to the alpha(1)A-subtype. (C) 1997 Elsevier Science Inc.