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

Abstract
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. In rat chromaffin cells maintained in culture for 1–7 days, ATP and UTP failed to evoke any detectable response. Guinea‐pig chromaffin cells responded to ATP (100 μM) 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. The response to ATP desensitized slowly, and had a reversal potential of 2.5 mV. The EC50 for ATP was 43 μM. The potency order for ATP analogues was 2‐MeSATP>ATP>ADP. Adenosine, UTP and α,β‐meATP were inactive. Suramin (100 μM) and Cibacron blue (50 μM) inhibited the ATP (100 μM)‐activated current by 51 and 47%, respectively. PPADS antagonized the response to ATP (100 μM) with an IC50 of 3.2 μM. The ATP concentration‐response curve shifted to the left at pH 6.8 (EC50, 19 μM) and right at pH 8.0 (EC50, 96 μM), without changing the maximal response. Zn2+ inhibited the response to ATP (100 μM) with an IC50 of 48 μM. 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. British Journal of Pharmacology (1999) 128, 61–68; doi:10.1038/sj.bjp.0702790