Kappa opioid receptors of human placental villi modulate acetylcholine release

Human placental villus tissue is non-innervated, yet it contains components of the opiate and cholinergic systems. We investigated whether opioids modulate a calcium dependent acetylcholine release from the villus tissue in a manner similar to that demonstrated by the parasympathetic nerve-smooth muscle junction. We reported that the kappa receptor agonist ethylketocyclazocine (EKC) inhibits acetylcholine release, and that the inhibition is reversed by the selective antagonist, Mr2266. Findings reported here substantiate the role of opioids as modulators of acetylcholine release from villus tissue. The nonselective agonist, morphine, also inhibits acetylcholine release. Inhibition caused by morphine is reversed by low concentrations of non-selective antagonists, naloxone and naltrexone. Naloxone at high concentrations potentiates the inhibition of acetylcholine release caused by morphine. In addition, the calcium channel blocker, diltiazem, was found to inhibit the release of acetylcholine. The combination of morphine and diltiazem resulted in a greater inhibition of acetylcholine release than by either alone. These results suggest that opiate cholinergic interactions occur in non-neural tissue with a mechanism similar to that known to occur at certain cholinergic synapses.