We have previously demonstrated that extracellular ATP elevates intracellular calcium ([Ca²⁺]_i) and stimulates calcium-activated K⁺ efflux from human placental cytotrophoblast cells in culture (Clarson et al. 2002). ATP can elevate [Ca²⁺]_i via P2X or P2Y purinergic receptor activation. Human placental tissue and trophoblast cells express, at the messenger RNA level, P2Y receptors (P2Y₁-P2Y₁₁) cloned from human tissue, and of the P2X receptors, P2X₁, P2X₂, P2X₄ and P2X₇ (Roberts et al. 2001; Roberts & Clarson, 2002). In order to determine which of the purinergic receptors have a functional role in the syncytiotrophoblast, the transporting epithelium of the human placenta, this study has examined selective purinergic agonist stimulation of ⁸⁶Rb (K⁺) efflux from cultured cytotrophoblast cells.

Cytotrophoblast cells were isolated from human term placenta and maintained in culture for 66 h, where they provide a model of the syncytiotrophoblast in placenta. Cells were loaded for 2 h with ⁸⁶Rb, washed, and ⁸⁶Rb efflux measured at 1 min intervals for 10 min. Eight selective agonists were applied at a concentration of 100 µM from 5 to 10 min of the efflux experiment.

Of the agonists studied ATP (a non-selective agonist), UTP (P2Y₂ and P2Y₄ specific), UDP and 5BrUTP (P2Y₆ specific agonists), BzATP (P2X₇ selective agonist) and ADP elevated ⁸⁶Rb efflux above control. 2MeADP and 2MeSATP (agonists for P2Y₁, P2Y₁₁, P2X₁, P2X₂ and P2X₄) had no effect at this concentration.

Based on published agonist selectivity (Burnstock, 1997) and receptor mRNA expression in placenta, the data reported here are consistent with P2Y₂, P2Y₄, P2Y₆ and P2X₇ receptors having a role in Ca²⁺-activated K⁺ efflux from the syncytiotrophoblast. These receptors may therefore be important in regulation of placental transport function.

This work was supported by the MRC.