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Thromboxane A2 mimetic (U-46619) induces hyperresponsiveness of smooth muscle in the canine bronchiole, but not in the trachea. 1996

S Takata, and H Aizawa, and M Shigyo, and K Matsumoto, and H Inoue, and H Koto, and N Hara
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

It has been reported that cholinergic agonists induce bronchoconstriction by directly stimulating M3 muscarinic receptors on the surfaces of smooth muscle cells. Although thromboxane A2 (TXA2) has been demonstrated to induce airway hyperresponsiveness to cholinergic agonists in vivo, it does not affect the contractile response of smooth muscle to cholinergic agonists in vitro. To investigate the causes for the discrepancy between the in vivo and in vitro data, we compared the effects exerted by a TXA2 mimetic, U-46619, on the smooth muscle of canine trachea and bronchiole. We measured the contractile response to exogenously applied acetylcholine (ACh) before and after the application of a subthreshold dose of U-46619. The subthreshold dose was determined as that dose which did not induce smooth muscle contraction, this being 10(-9) M in the present study. The contractile responses of tracheal strips to ACh were not affected by the subthreshold dose of U-46619. By contrast, the responses of bronchiolar rings were significantly enhanced by this subthreshold dose. The excitatory effect of U-46619 on the ACh-induced contraction was completely prevented by treatment with a TXA2 antagonist, BAY u3405. These results indicate that TXA2 directly increases the responsiveness of smooth muscle in the bronchiole, and suggest that increases in the responsiveness of small airways may play an important role in the development of the airway hyperresponsiveness induced by TXA2.

UI MeSH Term Description Entries
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D011450 Prostaglandin Endoperoxides, Synthetic Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds. Prostaglandin Endoperoxide Analogs,Prostaglandin Endoperoxide Analogues,Synthetic Prostaglandin Endoperoxides,Analogues, Prostaglandin Endoperoxide,Endoperoxide Analogues, Prostaglandin,Endoperoxides, Synthetic Prostaglandin
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D002227 Carbazoles Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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