Ca2+‐stores mobilization by diadenosine tetraphosphate, Ap4A, through a putative P2Y purinoceptor in adrenal chromaffin cells

Abstract

1 Diadenosine tetraphosphate (Ap₄A) evoked a concentration-dependent increase in cytosolic [Ca²⁺] in resting chromaffin cells. The EC₅₀ value for this action was 28.2 ± 6.6 μm. This effect was also produced by diadenosine pentaphosphate (Ap₅A) with an EC₅₀ of 50 ± 7 μm. 2 In contrast with this effect, pretreatment with Ap₄A or Ap₅A induced a 30% reduction in Ca²⁺ entry following 10 μm dimethylphenylpiperazinium. 3 The elevation in cytosolic [Ca²⁺] induced by AP₄A was persistent in ≅ 100 nm external [Ca²⁺] and was sensitive to depletion of internal Ca²⁺ stores by a bradykinin prepulse or whole cell depletion in Ca²⁺. 4 The effect of Ap₄A was mimicked and desensitized by the agonist adenosine 5′-O-(2-thiodiphosphate), and blocked by the P_2Y-receptor antagonist, cibachrome blue. The P_2X-receptor agonist α,β-methylene adenosine 5′-triphosphate was inactive both by itself or in combination with Ap₄A. This is compatible with a P_2Y-purinoceptor-mediated action.