We have demonstrated that adenosine did not produce any change of intracellular free Ca2+ concentration ([Ca2+]i) in oviductal ciliated cells; however, it increased the ATP-induced Ca2+ influx through the activation of protein kinase A (PKA). Uncaging Of IP3 and cAMP triggered a larger Ca2+ influx than did IP3 alone. Furthermore, the IP3 effect was abolished by Xestospongin C, an IP3 receptor blocker. Whole-cell recordings demonstrated the presence of an ATP-induced Ca2+ current, and the addition of adenosine increased the peak of this current. This effect was not observed in the presence of H-89, a PKA inhibitor. Using excised macro-patches of plasma membrane, IP3 generated a current, which was higher in the presence of the catalytic PKA subunit and this current was blocked by Xestospongin C. We show here that activation of plasma membrane IP3 receptors directly triggers Ca2+ influx in response to ATP and that these receptors are modulated by adenosine-activated PKA. (C) 2007 Elsevier Inc. All rights reserved.