The differential contribution of endogenous prostaglandins to the release of acetylcholine from the myenteric plexus of the guinea‐pig ileum

Abstract

1 Prostaglandin E (PGE) may be essential for maintaining the sensitivity of the myenteric plexus of guinea-pig ileum to nicotine. The contributions of prostaglandins to nervous activity evoked by different stimuli have now been investigated by measuring the amount of acetylcholine (ACh) released from the myenteric plexus of the guinea-pig ileum. 2 The amount of ACh released in response to dimethylphenylpiperazinium (DMPP) or substance P was depressed to about 40% of control by 2.8 pM indomethacin (Ind), whereas the release of ACh induced by 5-hydroxytryptamine (5-HT) was not affected. The inhibitory effects of Ind were oyercome by 14.3nm PGE2 .3 Mepacrine 5pgM, an inhibitor of phospholipase A2, depressed the release of ACh in response to DMPP and substance P to the same extent as Ind. These inhibitory effects of mepacrine were overcome by arachidonic acid (10pM), but not by arachidonic acid plus Ind. The release of ACh evoked by 5-HT or electrical field stimulation (EFS) was also inhibited to about 60% of control by mepacrine but these inhibitions were overcome by arachidonic acid (10pM) either in the absence or the presence of Ind. 4 The results suggest that endogenous prostaglandins and arachidonic acid contribute to the maintenance of the excitability of the myenteric plexus by DMPP and substance P. By contrast, the release of ACh induced by 5-HT and EFS may be regulated by arachidonic acid and not by prostaglandins.

The Effect of Exogenous Arachidonic Acid on Naloxone‐Induced Withdrawal Contractions of the Isolated Guinea‐Pig Ileum

“…The discrepancy between our finding and Capassso & Sorrentino's observation (1997) could be explained on the basis of a difference in the concentration of endogenous and exogenous arachidonic acid and also some other kinetic parameters (such as temperature). Although arachidonic acid at low concentration (10 mM) had a restorative effect on the electrical field stimulation-induced contraction of guinea-pig ileum which reduced by mepacrine (Takeuchi et al 1991), it appeared from the present data that arachidonic acid at high concentration (300 mM) not only did not potentiate withdrawal-induced contractures but also diminished their amplitude. In our previous study it was shown that arachidonic acid also reduced the response to acetylcholine but not to histamine (Mohammadi et al 1999).…”

“…Although the modulatory roles of endogenous arachidonic acid in the cholinergic system of various smooth muscles have previously been extensively investigated (Tamaoki et al 1987;Takeuchi et al 1991), only few reports have recently focussed on the role of arachidonic acid cascade in the modulation of opioidergic system (Capasso & Sorrentino 1997). With some evidence for induction of contractures in morphine withdrawal by endogenous arachidonic acid and inhibitory action of the exogenous arachidonic acid on Na π and Ca 2π conductances in neurones (Ordway et al 1991), it became of interest to verify whether exogenous arachidonic acid potentiates or attenuates the contractions of guinea-pig ileum elicited by naloxone after exposure to morphine.…”

Effects of H-89, an inhibitor of protein kinase A, on the acetylcholine release from myenteric plexus of guinea pig ileum.

“…PGI2 and PGE2 reversed the inhibitory effects of IND on the ACh release (Takeuchi et al, 1991;Fukunaga et al, 1993). PGs were reported to increase cyclic AMP level in various tissues including the peripheral neuronal tissues (Harris et al, 1979;Kalix, 1979).…”

“…Indomethacin (IND), an inhibitor of prostaglandin (PG) synthesis, inhibited nicotine and substance P-induced release of ACh from myenteric plexus of guinea pig ileum (Yagasaki et al, 1984;Takeuchi et al, 1991). PGI2 and PGE2 reversed the inhibitory effects of IND on the ACh release (Takeuchi et al, 1991;Fukunaga et al, 1993).…”

“…In the present study, we investigate the effect of H-89 on the ACh release induced by various stimuli to determine involvement of protein kinase A within the intracellular signal pathway from activation of receptors to release of ACh in the myenteric plexus of guinea pig ileum. Release of ACh induced by various stimuli:ACh released from tissue was collected in accordance with the method described by Takeuchi et al (1991). The preparations were equilibrated for 15min superfusion with Tyrode solution at a rate of 1-2ml/min.…”