title: Prostaglandin-induced inhibition of acetylcholine release from neuronal elements of dog tracheal tissue.
abstract: In an attempt to elucidate the possible roles of endogenous prostaglandins on the neuro-effector transmission in the dog trachea, effects of a prostaglandin antagonist (1-acetyl-2-[8-chloro-10, 11- dihydrobenz (b.f) (1.4) oxazepine-10-carbonyl]hydrazine (SC-19220] on the electrical and mechanical properties of smooth muscle cells and on neuro-effector transmission in the smooth muscle layer were studied by means of micro-electrode, double sucrose-gap, and tension recording methods. The levels of prostaglandins in the perfusate from the dog tracheal tissue were also determined using radioimmunoassay. Excitatory junction potentials (e.j.p.s) and twitch tension evoked by electrical field stimulation with short pulse duration (50-100 microseconds), which were abolished by tetrodotoxin (10(-7) M) or atropine (5 X 10(-6) M), showed gradual and continuous reduction in amplitude during superfusion with normal Krebs solution. Reduction in the amplitude of e.j.p.s occurred with no change in the membrane potential or membrane input resistance. SC-19220 (3.1 X 10(-5) M) did not modify the membrane potential, membrane input resistance or the sensitivity to acetylcholine of the smooth muscle cells. Yet, with application of SC-19220 (3.1 X 10(-6) M), gradual and continuous reductions in the amplitude of e.j.p.s and twitch contractions were no longer observed. With an increased concentration (3.1 X 10(-5) M), e.j.p.s and twitch contractions with a constant amplitude were obtained after the initial increase in the amplitude. When the amplitude of twitch contractions was stabilized by treatment with indomethacin (10(-5) M), low concentrations (10(-12) to 10(-10) M) of prostaglandin E2 (PGE2) or prostaglandin F2 alpha (10(-8) to 10(-6) M) markedly suppressed the amplitude of the twitch contractions. In some muscle preparations (ten out of twenty-two preparations examined), SC-19220 (3.1 X 10(-6) to 3.1 X 10(-5) M) produced a sustained contraction of the muscle, which was suppressed by atropine (5 X 10(-6) M) or PGE2 (10(-8) M). Following pre-treatment of the tissue with atropine (5 X 10(-6) M), SC-19220 did not evoke contracture. In the resting condition, 10-40 ng g-1 wet wt. tissue min-1 PGE or PGF was released into the perfusate from the tracheal muscle tissue of the control dog.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology*; D003989:Dibenzoxazepines / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D011458:Prostaglandins E / Q000032:analysis / Q000494:pharmacology; D011460:Prostaglandins F / Q000032:analysis / Q000494:pharmacology; D011863:Radioimmunoassay; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000502:physiology
chemical_list: D003989:Dibenzoxazepines; D011458:Prostaglandins E; D011460:Prostaglandins F; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D013779:Tetrodotoxin; D001285:Atropine; D015237:Dinoprost; D015232:Dinoprostone; D000109:Acetylcholine; D007213:Indomethacin