Open AccessPhospholipase A 2 augments contraction and intracellular calcium mobilization through thromboxane A 2 in bovine tracheal smooth muscle
Author(s) -
Takata Y.,
Nishimura Y.,
Maeda H,
Yokoyama M
Publication year - 1999
Publication title -
european respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.021
H-Index - 241
eISSN - 1399-3003
pISSN - 0903-1936
DOI - 10.1034/j.1399-3003.1999.14b26.x
Subject(s) - thromboxane a2 , medicine , endocrinology , phospholipase a2 , muscle contraction , nordihydroguaiaretic acid , contraction (grammar) , calcium in biology , acetylcholine , calcium , muscarinic acetylcholine receptor , chemistry , thromboxane , phospholipase c , biology , receptor , arachidonic acid , biochemistry , platelet , enzyme
Phospholipase A 2 (PLA 2 ) induces hyper‐sensitivity to muscarinic agonists in airway smooth muscle in vitro . The precise mechanism of this is unknown, but might involve altered calcium homeostasis. In order to elucidate the effects of PLA 2 , on bovine tracheal smooth muscle contraction, isometric tension and intracellular calcium concentration ([Ca 2+ ]i) were simultaneously measured in fura 2‐loaded muscle strips. A high concentration of PLA 2 (0.5 μg·mL ‐1 ) caused the muscle strips to contract, and this contractile response was significantly attenuated by pretreatment with indomethacin (IND; 10 μM), but not by nordihydroguaiaretic acid (NDGA; 10 μM). A low concentration of PLA 2 (0.02 μg·mL ‐1 ) did not directly contract muscle strips. However a low concentration PLA 2 significantly enhanced the threshold of the contractile response and that of the [Ca 2+ ]i response to acetylcholine (ACh), but not that of the response to a high K + concentration. These augmented responses to ACh returned to control levels after pretreatment with IND, a thromboxane (TX) synthetase inhibitor (OKY‐046; 10 μM) or a TXA 2 receptor antagonist (ONO‐3708; 10 μM), but not after NDGA pretreatment. These results suggest that a low concentration of phospholipase A 2 enhances smooth muscle responsiveness to acetylcholine by agonist‐mediated Ca 2+ mobilization facilitated by thromboxane A 2 . It is concluded that phospholipase A 2 plays an important role in bronchial hypersensitivity involving thromboxane A 2 . It remains to be examined whether similar abnormalities in calcium homeostasis and muscarinic receptor function or coupling are involved in the pathogenesis of asthma. Eur Respir J 1999; 14: 396–404.