- 作者: Yi-Ruu Lin; Pei-Chi Kao; Ming-Huan Chan
- 作者服務機構: a Institute of Medical Sciences, Tzu Chi University, No 701, Section 3, Chung Yang Road, Hualien, 970, Taiwan; ; b Department of Medicine, Tzu Chi University, Hualien, 970, Taiwan; ; c Department of Pharmacology, Tzu Chi University, Hualien, 970, Taiwan
- 中文摘要: --
- 英文摘要: Neuropeptide tachykinins, present within sensory nerves, have been implicated as neurotransmitters involved in nonadrenergic and noncholinergic airway muscle contraction. The signal transduction pathways of tachykinins on muscle contraction and Ca2+ mobilization were investigated in swine trachea. Tachykinins, substance P (SP) and neurokinin A (NKA), concentration (1 nM to 1 μM)-dependently induced contractile responses with removal of epithelium, whereas neurokinin B (NKB) did not alter the muscle tension. The SP- and NKA-evoked muscle contractions were inhibited by NK1-R antagonist L732138, but not by either NK2-R antagonist MDL29913 or NK3-R antagonist SB218795. Consistently, SP-elicited increase in [Ca2+ ]i was abolished by NK1-R antagonist, neither by NK2-R nor NK3-R antagonists. The SP-induced muscular responses were significantly inhibited by L-type Ca2+ channel blocker verapamil and withdrawal of external Ca2+. Caffeine (10 mM) or ryanodine (50 μM) also partly suppressed the SP-induced muscle responses. Inhibition of inositol 1,4,5-trisphosphate (InsP3) receptor with 2-APB (75 μM) potently attenuated SP-evoked Ca2+ mobilization and muscle contraction, which was further inhibited by 2-APB under Ca2+ -free external solution, but not completely. Unexpectedly, simultaneous blockade of InsP3 receptor and ryanodine receptor (RyR) by 2-APB and ryanodine enhanced SP-evoked muscle contraction and Ca2+ mobilization. This potentiation was virtually abolished by removal of external Ca2+ , suggesting native Ca2+ channels may contribute to this phenomenon. These results demonstrate that tachykinins produce a potent muscle contraction associated with Ca2+ mobilization via tachykinin NK1-R-dependent activation of multiple signal transduction pathways involving Ca2+ influx and release of Ca2+ from InsP3- and ryanodine-sensitive Ca2+ stores. Blockade of both InsP3 receptor and RyR enhances the Ca2+ influx through native Ca2+ channels in plasma membrane, which is crucial to Ca2+ signaling in response to NK1 receptor activation.
- 中文關鍵字: --
- 英文關鍵字: calcium, InsP3 receptor, myocyte, ryanodine receptor, tachykinin