Identification of L-type calcium channels associated with kappa opioid receptors in human placenta.

Transduction pathways of kappa receptor activation are not fully understood. Human placenta at term expresses only this type of opioid receptors and therefore offers a unique advantage for such investigations. It has previously been postulated that kappa receptors-mediated modulation of acetylcholine and placental lactogen release from human placentas require the influx of extracellular calcium and into the cells, possibly via voltage-dependent channels. We report here that another opioid-regulated placental function, the release of human chorionic gonadotropin (hCG), depends on extracellular calcium and the modality of its influx via L-type channels. Data presented demonstrated that the stimulation of hCG secretion by the kappa-selective agonist U69,593 was abolished in presence of either EGTA or the calcium channel blocker nifedipine. Results obtained on the combined effect of opioids and dihydropyridines indicated that placental kappa opioid receptors could be directly coupled to L-type calcium channels. The identification of the latter in villus membrane preparations, reported here for the first time, further contributes to the hypothesis that, in human placenta, kappa receptors-linked transduction mechanisms involve calcium and its conductance across villus membranes.