Tumor necrosis factor-alpha augments contraction and cytosolic Ca(2+) sensitivity through phospholipase A(2) in bovine tracheal smooth muscle.
To elucidate the effects of tumor necrosis factor-alpha (TNF-alpha) on tracheal smooth muscle contraction, we simultaneously measured isometric tension and intracellular Ca(2+) ([Ca(2+)](i)) in fura 2-loaded muscle strips. Smooth muscle force generation was evaluated in a high potassium (K(+); 20.0-80.0 mM) solution and with acetylcholine (3 nM-10 microM ). TNF-alpha (1-100 ng/ml) did not directly contract muscle strips. The contractile response to acetylcholine was enhanced after application of 10 ng/ml of TNF-alpha for 30 min but not the response of [Ca(2+)](i). The contractile response and the response of [Ca(2+)](i) to a high K(+) solution were not altered after application of TNF-alpha. The [Ca(2+)](i)-tension curve indicated that TNF-alpha enhanced the responsiveness of tracheal smooth muscle through the acetylcholine-mediated Ca(2+) sensitivity of intracellular contractile elements. The augmentation of the acetylcholine concentration-response curves for muscle tension in the presence of TNF-alpha (10 ng/ml) was inhibited in part after application of manoalide, a phospholipase A(2) inhibitor. We conclude that a low concentration of TNF-alpha enhances smooth muscle responsiveness to acetylcholine by agonist-mediated Ca(2+) sensitivity facilitated by phospholipase A(2).
Nakatani
Y
Y
First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, Japan.
Nishimura
Y
Y
Nishiuma
T
T
Maeda
H
H
Yokoyama
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D011189:Potassium Chloride; C045673:manoalide; D010741:Phospholipases A; D011796:Quinacrine; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2