抄録
The effects of extracellular ATP on β-adrenergic activation of CFTR Cl current (ICl,PKA) were studied in guinea-pig ventricular cells. The cells were initially exposed to 0.02-1 μM isoproterenol (ISO) for ~3 min to activate ICl,PKA, and then to 1-100 μM ATP in the presence of ISO. ATP was found to potentiate ICl,PKA, in most cells examined. In about 2/3 of them, however, the potentiation was preceded by an inhibition, ICl,PKA changing in a biphasic manner. The initial inhibition was due to stimulation of P1-purinoceptor by ATP, since the inhibition was attenuated by the blockers of this receptor type. With 50 μM ATP, the potentiation, on average, resulted in a 1.3 fold increase of the Cl conductance activated by ISO alone (0.02-1 μM). The effects of ADP and ATPγS on ICl,PKA were similar to those of ATP, while AMP and adenosine never potentiated ICl,PKA. Thus the potentiation was attributed to a stimulation of P2-purinoceptors. PDBu (0.5 μM), an activator of PKC, facilitated ICl,PKA, and in the presence of PDBu, ATP did not further potentiate ICl,PKA. When BIM (0.2 μM), an inhibitor of PKC, was present, ATP did not facilitate ICl,PKA. These findings suggested involvement of PKC in the observed ATP action. When ATP was removed in the presence of ISO, the potentiated ICl,PKA decreased (recovered) only slowly, and, if ATP was reapplied during this slowly recovering phase, the subsequent current potentiation was weak. Thus the stimulation of P2-purinoceptors by ATP facilitates the β-adrenergic activation of ICl,PKA through PKC activation, and this potential appears to persist for several min after removal of ATP. [Jpn J Physiol 54 Suppl:S104 (2004)]
