Pre- and postjunctional effects of prostaglandin E2, prostaglandin synthetase inhibitors and atropine on cholinergic neurotransmission in guinea pig ileum and bovine iris.

The effects of prostaglandin E2, arachidonic acid, prostaglandin synthetase inhibitors and atropine on cholinergic neuromuscular transmission were examined in isolated guinea pig ileum longitudinal muscle and bovine iris sphincter muscle. Prostaglandin E2 and arachidonic acid markedly enhanced contraction responses induced by nerve stimulation. In addition, prostaglandin E2, enhanced contraction responses to acetylcholine and direct muscle stimulation, approximately to the same extent as those to nerve stimulation. Prostaglandin synthetase inhibitors (indomethacin, meclofenamic acid and eicosatetraynoic acid) very effectively reduced contraction responses to nerve stimulation or acetylcholine, and they annulled the stimulant effect of arachidonic acid. Basal and nerve-induced efflux of acetylcholine from the eserinized tissues, as measured by mass fragmentography, was unaltered by prostaglandin E2, but diminished slowly during indomethacin. Subsequent prostaglandin administration caused a slight increase of nerve-induced release of acetylcholine. Atropine markedly increased overflow of acetylcholine form stimulated preparations of both types. This indicates that muscarinic receptors, causing diminished acetylcholine release in eserinized tissue, may be present also at postganglionic terminals. During atropine, an effect of prostaglandin E2 on acetylcholine release could still not be seen. Thus, using physicochemical determination of acetylcholine, we could not verify earlier reports, employing bioassay, claiming enhanced release of transmitter during prostaglandin E2 treatment. However, it seems likely that prostaglandin E2 takes part in the regulation of contractility and tone of the smooth muscle cells.