期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 599, 期 1-3, 页码 137-145出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.09.045
关键词
Smooth muscle; Urinary bladder; Myogenic contraction; Signal transduction; ROCK [rhoA kinase]; Rabbit
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-59620]
- Edwin Beer Research Program in Urology
- New York Academy of Medicine
Urinary bladder wall muscle (i.e., detrusor smooth muscle; DSM) contracts in response to a quick-stretch, but this response is neither fully characterized, nor completely understood at the subcellular level. Strips of rabbit DSM were quick-stretched (5 ms) and held isometric for 10 s to measure the resulting peak quick-stretch contractile response (PQSR). The ability of selective Ca2+ channel blockers and kinase inhibitors to alter the PQSR was measured, and the phosphorylation levels of myosin light chain (MLC) and myosin phosphatase targeting regulatory subunit (MYPT1) were recorded. DSM responded to a quick-stretch with a biphasic response consisting of an initial contraction peaking at 0.24 +/- 0.02-fold the maximum KCl-induced contraction (F-o) by 1.48 +/- 0.17 s (PQSR) before falling to a weaker tonic (10 s) level (0.12 +/- 0.03-fold F-o). The PQSR was dependent on the rate and degree of muscle stretch, displayed a refractory period, and was converted to a sustained response in the presence of muscarinic receptor stimulation. The PQSR was inhibited by nifedipine, 2-aminoethoxydiphenyl borate (2-APB), 100 mu M gadolinium and Y-27632, but not by atropine, 10 mu M gadolinium, LOE-908, cyclopiazonic acid, or GF-109203X. Y-27632 and nifedipine abolished the increase in MLC phosphorylation induced by a quick-stretch. Y-27632, but not nifedipine, inhibited basal MYPT1 phosphorylation, and a quick-stretch failed to increase phosphorylation of this rhoA kinase (ROCK) substrate above the basal level. These data support the hypothesis that constitutive ROCK activity is required for a quick-stretch to activate Ca2+ entry and cause a myogenic contraction of DSM. (C) 2008 Elsevier B.V. All rights reserved.
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