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 expression 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 failed to evoke any detectable response. 3. Guinea-pig chromaffin cells responded to ATP (100 microM) with a rapidly activating inward current. The amplitude of the response to ATP increased over the period cells were maintained in culture and so did the number of cells giving a detectable response, with 69% of cells responding after >/=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 microM. The potency order for ATP analogues was 2-MeSATP>ATP>ADP. Adenosine, UTP and alpha,beta-meATP were inactive. 5. Suramin (100 microM) and Cibacron blue (50 microM) inhibited the ATP (100 microM)-activated current by 51 and 47%, respectively. PPADS antagonized the response to ATP (100 microM) with an IC50 of 3.2 microM. 6. The ATP concentration-response curve shifted to the left at pH 6.8 (EC50, 19 microM) and right at pH 8.0 (EC50, 96 microM), without changing the maximal response. Zn2+ inhibited the response to ATP (100 microM) with an IC50 of 48 microM. 7. This study indicates that expression of ATP-gated cation channels in chromaffin cells is species dependent. The P2X receptors in guinea-pig chromaffin cells show many characteristics of the P2X2 receptor subtype.