Involvement of different Ca2+ pools during the canine bronchial sustained contraction in Ca2+-free medium:: lack of effect of PKC inhibition

被引:15
作者
Bazán-Perkins, B
Carbajal, V
Sommer, B
Macías-Silva, M
Gonzalez-Martinez, M
Valenzuela, F
Daniel, EE
Montano, LM
机构
[1] Inst Nacl Enfermedades Resp, Dept Invest Asma, Mexico City 14080, DF, Mexico
[2] Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City 04510, DF, Mexico
[3] McMaster Univ, Dept Biomed Sci, Hamilton, ON L8S 4L8, Canada
[4] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Bioenerget, Mexico City 04510, DF, Mexico
关键词
protein kinase C; intracellular Ca2+; bronchial sustained contraction; Ca2+-free medium;
D O I
10.1007/PL00005294
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We evaluated the role of protein kinase C (PKC) in the sustained bronchial contraction (SBC) induced by carbachol (Cch) or histamine in a Ca2+-free medium and the possibility that each agonist uses a different Ca2+ store for this response. We studied third-order bronchi and airway smooth muscle (ASM) from first-order bronchi dissected free of cartilage and epithelium. Bronchial and ASM responsiveness to Cch or histamine were evaluated in Krebs solution (2.5 mM Ca2+) and in Ca2+-free medium. Cch and histamine induced an SEC in bronchial tissues in Ca2+-free medium. In ASM each agonist produced a transient contraction, but the response to histamine was much smaller. Cch induced a concentration-dependent accumulation of inositol phosphates (IPs) in both bronchi and ASM; however, histamine did not induce significant accumulation of IPs. Repeated exposure to histamine in bronchial rings abolished contractile responses in Ca2+-free media, but Cch added afterwards still produced a sustained contraction. This response was blocked when bronchial tissues were preincubated with 10 mu M cyclopiazonic acid (CPA). Brief incubation of these preparations with a high EGTA concentration (1 mM) abolished the histamine-induced SEC. The SEC induced by Cch or histamine in Ca2+-free medium was not affected by the preincubation of the tissues with calphostin C, chelerythrine or staurosporine. We concluded that Cch mobilizes Ca2+ from two different sources during the SEC in Ca2+-free medium: from a CPA-sensitive one from sarcoplasmic reticulum (SR) and from a putative extracellular membrane Ca2+ pool sensitive to 1 mM EGTA, and neither process involved PKC activation. Histamine appeared to utilize the extracellular membrane pool only.
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页码:567 / 573
页数:7
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