Prostaglandin E2 stimulation of acetylcholine release from guinea pig myenteric plexus neurons

Prostaglandins are widely distributed within the gastrointestinal tract and have important effects on gastrointestinal motility. Although actions upon gastrointestinal smooth muscle have been demonstrated for prostaglandins (PG), neural mechanisms may also be important. The effects of PGE2 on acetylcholine (ACh) release were studied using guinea pig myenteric plexus neurons in primary culture. PGE stimulated the release of ACh in a dose-dependent manner, with a median effective dose (ED50) of 0.8 x 10(-6) M. Involvement of L-type calcium channels was implied by the sensitivity of PGE2-stimulated ACh release to omega conotoxin or diltiazem. In addition, ACh release stimulated by PGE2 could be inhibited by co-incubation with dideoxyadenosine or Rp-cAMPS, agents that act upon cyclic adenosine monophosphate (cAMP)-dependent signaling pathways. PGE2 has direct effects upon myenteric neurons to stimulate cholinergic transmission.