Extracellular ATP-induced calcium channel inhibition mediated by P1/P2Y purinoceptors in hamster submandibular ganglion neurons

1 The presence and profile of purinoceptors in neurons of the hamster submandibular ganglion (SMG) have been studied using the whole-cell configuration of the patch-clamp technique. 2 Extracellular application of adenosine 5-triphosphate (ATP) reversibly inhibited voltage-dependent Ca2+ channel (VDCC) currents (I-Ca) via G(i/o)-protein in a voltage-dependent manner. 3 Extracellular application of uridine 5'-triphosphate (UTP), 2-methylthioATP (2-MeSATP), alpha,beta-methylene ATP (alpha,beta-MeATP) and adenosine 5'-diphosphate (ADP) also inhibited I-Ca. The rank order of potency was ATP = UTP > ADP > 2-MeSATP = alpha,beta-MeATP. 4 The P2 purinoceptor antagonists, suramin and pyridoxal-5-phosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS), partially antagonized the ATP-induced inhibition of I-Ca, while coapplication of suramin and the P1 purinoceptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), virtually abolished I-Ca inhibition. DPCPX alone partially antagonized I-Ca inhibition. 5 Suramin antagonized the UTP-induced inhibition of I-Ca, while DPCPX had no effect. 6 Extracellular application of adenosine (ADO) also inhibited I-Ca in a voltage-dependent manner via G(i/o)-protein activation. 7 Mainly N- and P/Q-type VDCCs were inhibited by both ATP and ADO via G(i/o)-protein betagamma subunits in seemingly convergence pathways.