Functional cross talk after activation of P2 and P1 receptors in oviductalciliated cells

The presence of ATP and adenosine receptors and their role in controlling c iliary activity in oviductal ciliated cells was studied by measuring the ci liary beat frequency (CBF) in oviductal tissue cultures. ATP, adenosine, an d related compounds increased the CBF in a dose-dependent manner. We establ ished that P2 receptors of subtype 2Y(2) and P1 receptors of subtype A(2a) mediated the responses to ATP and adenosine, respectively. We found evidenc e to suggest that stimulation of ciliary activity by ATP requires D-myoinos itol 1,4,5-trisphosphate [Ins(1,4,5)P-3] metabolism, intracellular Ca2+ mob ilization, and protein kinase C activation. On the other hand, the adenosin e effect is mediated by activation of a G(s) protein-dependent pathway that enhances cAMP intracellular levels. To study the interaction between P2 an d P1 receptors, cells were stimulated simultaneously with both agonists. We observed a synergistic increase of the CBF even at agonist concentrations (100 nM) that did not produce a significant response when added separately to the culture. Furthermore, a blocker of the cAMP pathway produced a reduc tion of the ATP response, whereas a blocker of the Ins( 1,4,5) P3 pathway a lso produced an inhibition of the adenosine response. Our evidence demonstr ates that both ATP and adenosine receptors are present in a single ciliated cell and that a mechanism of cross talk could operate in the transduction pathways to control ciliary activity.