Actions of indomethacin and prostaglandins on neuro-effector transmission in the dog trachea.

Neuro-effector transmission in the smooth muscle layer of the dog trachea was studied in vitro using the micro-electrode and double sucrose gap methods.1. Electrical field stimulations with short duration (50-100 musec) applied to the whole tissue produced an excitation of the intrinsic nerves, and evoked excitatory junction potentials (e.j.p.s) followed by twitch tension development and subsequent long lasting relaxation of the smooth muscle tissue.2. The effects of field stimulations were abolished by tetrodotoxin (2 x 10(-7)m), and atropine (1.7 x 10(-5)m) selectively blocked both the e.j.p. and twitch tension. On the other hand, propranolol (1.9 x 10(-5)m) suppressed the generation of the prolonged relaxation evoked by the field stimulations.3. E.j.p.s recorded by the double sucrose gap method showed gradual and continuous reduction in amplitude during prolonged exposure in Krebs solution (1-2 hr), and there were no changes in the membrane potential or in the input membrane resistance.4. With application of indomethacin (10(-5)m), a gradual and continuous reduction in the amplitude of e.j.p. was no longer observed, and (after the initial increase in the amplitude) e.j.p.s with a constant amplitude were obtained during 1-1.5 hr. Indomethacin (10(-5)m) modified neither the resting membrane potential nor the input membrane resistance of smooth muscle cells.5. After pre-treatment with indomethacin, low concentrations (10(-11)-10(-8)m) of prostaglandin E(1) or E(2) (PGE series) markedly suppressed the amplitude of e.j.p. with no changes in the resting membrane potential or in the input membrane resistance.6. During the repetitive field stimulation at the stimulus frequency of 0.1-1 Hz, the amplitude of the e.j.p.s was gradually reduced (the depression process). The depression was not affected by applications of prostaglandins, indomethacin or alpha- and beta-adrenoceptor blockers.7. These results indicate that in the dog tracheal smooth muscles, the endogenous PGE series may play an important role in feed-back inhibitory mechanisms, at the nerve terminals related to acetylcholine release.