Neural and myogenic effects of cyclooxygenase products on canine bronchial smooth muscle.
In canine bronchi bathed in 10(-6) M indomethacin (IDM), prostaglandin (PG) E2 inhibited electrical field stimulation (EFS)- and acetylcholine (ACh)-mediated contractions and excitatory junction potentials (EJP) in a concentration-dependent manner without altering the resting membrane potential. EFS-induced EJPs were abolished at 10(-7) M PGE2, which shifted responses to ACh 10-fold rightward. Thus PGE2 predominantly inhibited the release of ACh and secondarily decreased smooth muscle response to ACh. U-46619, an analogue of thromboxane A2 (TxA2), initiated tetrodotoxin- and atropine-insensitive contractions in a concentration-dependent manner. U-46619 (10(-9) M) did not alter significantly EFS- or ACh-stimulated contractions and potentiated EFS amplitude of EJPs without depolarizing muscle cells. Either prejunctional activation of ACh release by TxA2 or postjunctional potentiation of the response to ACh can explain these findings. U-46619 (> or = 10(-8) M) depolarized the membrane potential, initiating oscillations accompanied by a large contraction. Addition of 10(-8) M nitrendipine, but not tetraethylammonium (25 mM), blocked the oscillations selectively. Other prostanoids (PGD2, PGI2, and PGF2 alpha) had no significant effects on canine bronchi. In the absence of IDM, PGE2 accumulated, EFS contractions decreased with time, and EJPs disappeared. We conclude that in canine bronchi PGE2 predominantly inhibits ACh release and endogenous PGE2 acts similarly, whereas TxA2 excites, probably at postjunctional sites.
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
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Abela
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Daniel
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D017629:Gap Junctions / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D009424:Nervous System Physiological Phenomena; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology; D013928:Thromboxane A2 / Q000494:pharmacology
D011453:Prostaglandins; D013928:Thromboxane A2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone