Pathways for α₁-adrenoceptor and its subtypes to influence the β-adrenoceptor mediated positive inotropic response of heart in rats

The activation of α₁-adrenoceptor (α₁-AR) or its subtypes affecting the β-adrenoceptor (β-AR) mediated positive inotropic response of heart in rats had been demonstrated. The possible pathways for those interactions were explored. The results showed that activation of both α₁-AR and β-AR by norepinephrine (NE) or isoprenaline (Iso) plus phenylephrine (PE) induced less cAMP accumulation than that of only β-AR. α₁-AR subtype selective antagonist WB4101 (1 nmol · L^-1) potentiated the β-AR mediated stimulation of cAMP accumulation, while α(1B)-AR subtype selective alkylating agent chloroethylclonidine (CEC, pre-incubation at 20 μmol · L^-1) inhibited it. Activation of α₁-AR, however, did not influence the forskolin-induced cAMP production. The radioligand binding assays showed that activation of α₁-AR or either subtypes had no effect on the maximal binding concentration (B(max)) and the affinity (K(d)) of [¹²⁵I]pindolol to β-AR. The Iso inhibition curve was shifted to the right in the presence of 100 μmol · L^-1 GTP, and activation of α₁-AR showed no effect on the shift. Thus, the α(1B)-AR enhanced the β-AR mediated cAMP production, while the α(1A)-AR inhibited. And α(1A)-AR played a dominant role while both subtypes were activated simultaneously. The results suggested that the pathway for α₁-AR and its subtype to influence the β-AR mediated inotropic response located at the signal transduction before the activation of adenyl cyclase. Activation of α₁-AR and its subtypes might change the activity of G(s) protein.