The presence of beta2-adrenoceptors sensitizes alpha2A-adrenoceptors to desensitization after chronic epinephrine treatment.

Background: In addition to the regulation of blood pressure, alpha2- and beta-adrenoceptor (AR) subtypes play an important role in the modulation of noradrenergic neurotransmission in the human CNS and PNS. Several studies suggest that the alpha2-AR responsiveness in cells and tissues after chronic epinephrine (EPI) or norepinephrine (NE) exposure may vary, depending on the beta-AR activity present there. Recently, we reported that in BE(2)-C human neuroblastoma cells (endogenously expressing alpha2A- and beta2-AR), chronic EPI treatment (300 nM) produced a dramatic beta-adrenoceptor-dependent desensitization of the alpha2A-AR response.

Desensitization of alpha 2A-adrenoceptor signalling by modest levels of adrenaline is facilitated by beta 2-adrenoceptor-dependent GRK3 up-regulation.

(1) Adrenaline (ADR) and noradrenaline (NA) can simultaneously activate inhibitory alpha(2)- and stimulatory beta-adrenoceptors (AR). However, ADR and NA differ significantly in that ADR is a potent beta(2)-AR agonist while NA is not. Only recently has the interaction resulting from the simultaneous activation of alpha(2)- and beta(2)-AR been examined at the cellular level to determine the mechanisms of alpha(2)-AR regulation following concomitant activation of both alpha(2)- and beta(2)-ARs by chronic ADR.