Atypical β- and α(2)-adrenoceptor Activation, Dibutyryl cAMP and Iloprost Stimulate [(45)Ca(2+)] Uptake by Human Platelets.
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.
Metabolic Unit, Department of Chemical Pathology and Human Metabolism, Royal Free Hospital & School of Medicine, Pond Street, London, NW3 2QG, UK.
J
J
Gill
P
P
Dandona
J Y
JY
Jeremy