Pre- and postjunctional effects of a thromboxane mimetic in canine bronchi.
Thromboxane A2 is believed to participate in causation of hyperreactivity of airway smooth muscle (ASM). We therefore investigated the effects of a thromboxane mimetic (U-46619) on isolated ring segments of canine bronchial ASM (3rd to 5th order). U-46619 (10(-9)-10(-5) M) was found to elicit tonic contraction, membrane depolarization, and oscillations in membrane potential. These effects were sensitive to blockade of thromboxane receptors (using 10(-8) M L 670, 596); the mechanical response was insensitive to 3 x 10(-8) M atropine, 10(-7) M nitrendipine, or exposure to Ca(2+)-free media [(containing 0.5 mM ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)]. U-46619 also potentiated electrical field stimulation-elicited contractions and excitatory junction potentials without altering the sensitivity to carbachol. This potentiation was also sensitive to L 670,596 but not to blockade of adrenoceptors (using phentolamine plus propranolol). We conclude that canine bronchial ASM possesses both prejunctional and postjunctional thromboxane receptors. The former potentiate cholinergic neurotransmission through a mechanism not involving adrenoceptors. The latter excite the ASM through a mechanism not involving muscarinic receptors and that utilizes intracellular Ca2+ (rather than extracellular Ca2+). Excitation-contraction coupling was found to be pharmacomechanical in nature (rather than electromechanical).
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
L J
LJ
Janssen
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Daniel
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors
D002227:Carbazoles; D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; C061299:L 670596; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid