Atypical β- and α(2)-adrenoceptor Activation, Dibutyryl cAMP and Iloprost Stimulate [(45)Ca(2+)] Uptake by Human...

The effect of a range of α- and β-adrenoceptor agonists and antagonists on the in vitro uptake of [(45)Ca(2+)] by human platelets was investigated. Isoprenaline and adrenaline stimulated [(45)Ca(2+)] uptake. Isoprenaline-stimulated ([(45)Ca(2+)] uptake was inhibited by β-adrenoceptor antagonists (mabuterol [β(2)] > metoprolol [β(1)] > atenolol [β(1)] > pindolol [β(1)/β(2)]), but not by yohimbine [αz] or prazosin [αll. Adrenaline-stimulated [(45)Ca(2+)] uptake was inhibited (and in this order of potency) by yohimbine, mabuterol, metoprolol, prazosin, atenolol and pindolol. [(45)Ca(2+)] uptake was stimulated by β-adrenoceptor agonists (BRL37344 [β(3)] > terbutaline [β(2)] > xamoterol [β(1)] > salbutamol [β(2)]). Ca(2+) ionophore A23187-stimulated [(45)Ca(2+)] uptake was unaffected by pindolol, atenolol, metoprolol or mabuterol, indicating that these antagonists were not exerting nonspecitic inhibitory effects. [(45)Ca(2+)] uptake was also stimulated by dibutyryl cAMP and by iloprost (a stable prostacyclin analogue and stimulator of cAMP synthesis). It is concluded that: (1) β- adrenoceptor-linked Ca(2+) uptake is mediated by an atypical β-adrenoceptor, possibly of a β(3)-subtype; (2) the stimulatory action of β-adrenoceptor activation and prostacyclin may be mediated by adenylate cyclase, and (3) the paradoxical finding that both α- and β-adrenoceptor activation, cAMP and stimulators of CAMP elicit [(45)Ca(2+)] uptake suggests that the Ca(2+) mobilisation monitored by the present methodology is not associated with platelet aggregation but to adrenoceptor activation per se and possibly other signal transduction mechanisms that occur at the plasmalemma.