ACTIVATION BY ATP OF A P-2U NUCLEOTIDE RECEPTOR IN AN EXOCRINE CELL

1 We employed the perforated patch whole-cell technique to investigate the effects of ATP and other related nucleotides on membrane conducta nces in avian exocrine salt gland cells. 2 ATP (10 mu M - 1 mM) evoked an increase in maxi-K+ and Cl- conductances with a reversal potential of -35 mV. At lower concentrations of ATP (less than or equal to 100 mu M) responses were generally oscillatory with a sustained response o bserved at higher concentrations (greater than or equal to 200 mu M). 3 Both oscillatory and sustained responses were abolished by the remov al of bath Ca2+. In cells preincubated in extracellular saline contain ing reduced Ca2+, the application of ATP resulted in a transient incre ase in current. 4 As increasing concentrations of ATP (and related nuc leotides) evoked a graded sequence of events with little run-down we w ere able to establish a rank order of potency in single cells. The ord er of potency of ATP analogues and agonists of the various P-2-recepto r subtypes was UTP > ATP = 2-methylthio-ATP > ADP. Adenosine (1 mu M - 1 mM), AMP (1 mu M - 1 mM), alpha,beta-methylene-ATP (1 mu M - mM) an d beta,gamma-methylene-ATP (1 mu M - 1 mM) were without effect. 5 In c onclusion, although unable to preclude a role for a P-2Y-receptor, our results suggest that ATP binds to a P-2U-receptor increasing [Ca2+](i ) and subsequently activating Ca2+-sensitive K+ and Cl- currents.