CA-2+-STORES MOBILIZATION BY DIADENOSINE TETRAPHOSPHATE, AP4A, THROUGH A PUTATIVE P2Y PURINOCEPTOR IN ADRENAL CHROMAFFIN CELLS

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-mu-M. This effect was also produced by diadenosine pentaphosphate (Ap5A) with an EC50 of 50 +/- 7-mu-M. 2 In contrast with this effect, pretreatment with Ap4A or Ap5A induced a 30% reduction in Ca2+ entry following 10-mu-M dimethylphenylpiperazinium. 3 The elevation in cytosolic [Ca2+] induced by Ap4A was persistent in almost-equal-to 100 nm external [Ca2+] and was sensitive td 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 P2Y-receptor antagonist, cibachrome blue. The P2X-receptor agonist alpha,beta-methylene adenosine 5'-triphosphate was inactive both by itself or in combination with Ap4A. This is compatible with a P2Y-purinoceptor-mediated action.