Possible subdivision of postsynaptic α-adrenoceptors mediating pressor responses in the pithed rat

Abstract

Additional evidence has been obtained indicating a possible subclassification of postsynaptic α-adrenoceptors into α₁ and α₂-subtypes. The pressor responses to the α-adrenoceptor agonists L-phenylephrine and guanfacine were quantified after i.v. administration to pithed rats. The α-sympatholytic drug yohimbine (1 mg/kg) displaced both dose-response curves to the right, but the effect was greatest for guanfacine. After prazosin (0.1 mg/kg) a 53-fold shift to the right was noticed for the dose-response characteristic of L-phenylephrine. Prazosin antagonized the effect of only the higher doses of guanfacine. The findings indicate that L-phenylephrine and prazosin preferentially interact with α₁-adrenoceptors as agonist and antagonist, respectively. Yohimbine proved less selective than prazosin, but preferentially blocks postjunctional α₂-adrenoceptors in the vascular wall. The results obtained with guanfacine may be interpreted to indicate that this drug acts on α₂-adrenoceptors at lower doses and additionally stimulates α₁-adrenoceptors at higher ones. Preliminary findings with corynanthine and rauwolscine support this interpretation.