Atypical β and α₂-adrenoceptor activation, dibutyryl cAMP and iloprost stimulate [⁴⁵ca²⁺] uptake by human platelets

The effect of a range of α and βadrenoceptor agonists and antagonists on the in vitro uptake of [⁴⁵Ca²⁺] by human platelets was investigated. Isoprenaline and adrenaline stimulated [⁴⁵Ca²⁺] uptake. Isoprenaline-stimulated ([⁴⁵Ca²⁺] uptake was inhibited by βadrenoceptor antagonists (mabuterol [β₂] > metoprolol [β₁] > atenolol [β₁] > pindolol [β₁/β₂]), but not by yohimbine [αz] or prazosin [αll. Adrenaline-stimulated [⁴⁵Ca²⁺] uptake was inhibited (and in this order of potency) by yohimbine, mabuterol, metoprolol, prazosin, atenolol and pindolol. [⁴⁵Ca²⁺] uptake was stimulated by βadrenoceptor agonists (BRL37344 [β₃] > terbutaline [β₂] > xamoterol [β₁] > salbutamol [β₂]). Ca²⁺ ionophore A23187-stimulated [⁴⁵Ca²⁺] uptake was unaffected by pindolol, atenolol, metoprolol or mabuterol, indicating that these antagonists were not exerting nonspecitic inhibitory effects. [⁴⁵Ca²⁺] 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 Ca²⁺ uptake is mediated by an atypical βadrenoceptor, possibly of a β₃-subtype; (2) the stimulatory action of βadrenoceptor activation and prostacyclin may be mediated by adenylate cyclase, and (3) the paradoxical finding that both α and βadrenoceptor activation, cAMP and stimulators of CAMP elicit [⁴⁵Ca²⁺] uptake suggests that the Ca²⁺ 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.