Contribution of prostaglandins to the activity of guinea-pig phrenic and chicken oesophageal parasympathetic nerves.

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Abstract
In order to clarify the role of prostaglandins (PGs) in the activity of cholinergic neurones other than the ileal myenteric plexus, the effects of indomethacin (IND) and PGE2 on the contractile responses and the release of acetylcholine (ACh) induced by electrical stimulation were investigated in isolated guinea-pig phrenic nerve-diaphragm and chicken parasympathetically innervated oesophagus preparations. In the guinea-pig phrenic nerve-diaphragm preparations, IND at 56 .mu.M did not affect the twitch responses induced by direct or indirect electrical stimulation. PGE2 at 1 .mu.g/ml augmented the twitch responses induced by direct or indirect stimulation of submaximal, but not of supramaximal intensity. The amounts of ACh released from the phrenic nerve by electrical stimulation were unaffected by IND (56 .mu.M). PGE2 (0.01 .apprx. .mu.g/ml) inhibited the ACh release by the nerve stimulation of high frequency (50 Hz) in a concentration-dependent manner. The inhibitory effect of PGE2 was less clear on the ACh release by lower frequency (1 Hz). Neither IND nor PGE2 affected the ACh release induced by 40 mM-K+. In the chicken parasympathetically innervated oesophagus preparation, IND (2.8 .apprx. 5.6 .mu.M) augmented the twitch responses induced by the nerve stimulation at a frequency of 0.017 Hz, but not those produced by train pulse (5 sec at a frequency of 1 or 10 Hz). This augmentation was reversed by the application of PGE2 at 10 ng/ml. PGE2 at 10 ng/ml produced a transient inhibition of the twitch responses induced by 0.017 Hz or train pulses, IND (2.8 .mu.M) significantly increased the ACh release evoked by the parasympathetic nerve stimulation at a frequency of 10 Hz. This increase was reversed by the application of PGE2 at 10 ng/ml. The ACh release by the nerve stimulation at a frequency of 1 Hz was slightly increased by IND (2.8 .mu.M). PGE2 at 10 ng/ml significantly decreased the ACh release evoked by the nerve stimulation at a frequency of either 1 or 10 Hz. The results indicate that in the guinea-pig phrenic nerve-diaphragm and chicken parasympathetically innervated oseophagus preparations, PG has both neurotropic and musculotropic actions. Thus, it inhibits the release of ACh evoked by the electrical nerve stimulation acting on the nerve on one hand and augments the twitch responses acting directly on the muscle on the muscle cell on the other. Since IND did not affect the electrically evoked release of ACh from the phrenic nerve, whereas it affected the release from chicken parasymphathetic nerve, it is suggested that endogenous PGs are physiologically less important in regulating the activity of motor nerve.

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