Ca²⁺‐stores mobilization by diadenosine tetraphosphate, Ap<inf>4</inf>A, through a putative P<inf>2Y</inf> purinoceptor in adrenal chromaffin cells

Abstract

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. In contrast with this effect, pretreatment with Ap4A or Ap5A induced a 30% reduction in Ca2+ entry following 10 μm dimethylphenylpiperazinium. 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+. The effect of Ap4A was mimicked and desensitized by the agonist adenosine 5′‐O‐(2‐thiodiphosphate), and blocked by the P2Y‐receptor antagonist, cibachrome blue. The P2X‐receptor agonist α,β‐methylene adenosine 5′‐triphosphate was inactive both by itself or in combination with Ap4A. This is compatible with a P2Y‐purinoceptor‐mediated action.