Rat chromaffin cells lack P2X receptors while those of the guinea-pig express a P2X receptor with novel pharmacology

1 Whole-cell patch-clamp recording was used to determine the functional exp ression and pharmacological properties of P2X receptors in chromaffin cells dissociated from adrenal medullae of rats and guinea-pigs. 2 In rat chromaffin cells maintained in culture for 1-7 days, ATP and UTP f ailed to evoke any detectable response. 3 Guinea-pig chromaffin cells responded to ATP (100 mu M) with a. rapidly a ctivating inward current. The amplitude of the response to ATF increased ov er the period cells were maintained in culture and so did the number of cel ls giving a detectable response, with 69%, of cells responding after greate r than or equal to 4 days of culture. 4 The response to ATP desensitized slowly, and had a reversal potential of 2.5 mV. The EC50 for ATP was 43 mu M. The potency order for ATP analogues w as 2-MeSATP> ATP>ADP. Adenosine, UTP and alpha,beta-meATP were inactive. 5 Suramin (100 mu M) and Cibacron blue (50 mu M) inhibited the ATP (100 mu M)-activated current by 51 and 47%, respectively. PPADS antagonized the res ponse to ATP (100 mu M) With an IC50 of 3.2 mu M 6 The ATP concentration-response curve shifted to the left at pH 6.8 (EC50, 19 mu M) and right at pH 8.0 (EC50, 96 mu M), without changing the maximal response. Zn2+ inhibited the response to ATP (100 mu M) with an IC50 of 48 mu M. 7 This study indicates that expression of ATP-gated cation channels in chro maffin cells is species dependent. The P2X receptors in guinea-pig chromaff in cells show many characteristics of the P2X(2) receptor subtype.