Modulation by prostaglandins of the release of acetylcholine and noradrenaline in guinea-pig isolated ileum

Abstract

The effects of prostaglandin (PG) E2, PGF2alpha and indomethacin on the release of acetylcholine (ACh), noradrenaline (NA) and prostaglandin-like substances from the isolated guinea-pig ileum and its longitudinal muscle-myenteric plexus preparation were investigated. The output of ACh and PGs was determined by a bioassay and the output of NA by an isotope technique. The output of ACh, both resting and stimulated, was decreased by indomethacin (1 micron) especially after a longer exposure. The output of ACh was increased by PGE2 (6 nM) but not by PGF2alpha. This increase was inversely related to the initial level of ACh output; thus, it was marked only in the preparations with low initial output of ACh. Prostaglandin-like substances released from the ileum were mainly of the E type and their output only partially correlated with contractions and with the output of ACh. The stimulated outflow of NA at a frequency of 5 Hz was increased by indomethacin (50 micron) and decreased by PGE2 (30 nM). PGF2alpha had no effect. These results suggest that PGE2 might act physiologically as a modulator of cholinergic transmission whereas its effect on adrenergic transmission could be of a pharmacological nature.