@article{oai:nagoya.repo.nii.ac.jp:00001357, author = {Oguma, Tetsuya and Kume, Hiroaki and Ito, Satoru and Takeda, Naoya and Honjo, Haruo and Kodama, Itsuo and Shimokata, Kaoru and Kamiya, Kaichiro and 神谷, 香一郎}, issue = {2}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, month = {Feb}, note = {To determine the involvement of Ca2+ sensitization in b-adrenergic action, we examined the relationship between isometric tension and intracellular Ca2+ concentration (F340/F380) in the inhibitory action of isoproterenol (ISO) against methacholine (MCh)- induced contraction, using fura-2 loaded tracheal smooth muscle.\nISO reduces contraction more than Ca2+ concentration. This phenomenon was mimicked by forskolin and db-cAMP. In contrast, an inhibition in tension by SKF- 96365, a non-selective Ca2+ channel inhibitor, was associated with that in F340/F380, different from ISO. In the presence of Rp-cAMP, a membrane-permeable inhibitor of protein kinase A (PKA), ISO caused an equivalent relaxation with a less reduction in F340/F380. The effects of ISO were not affected in the presence of Y-27632, an inhibitor of Rho-kinase, and bisindolylmaleimide, an inhibitor of protein kinase C. Even removal of Ca2+ from the extracellular surface, the effects of ISO was not affected. ISO also inhibits high K+-induced contraction without lowering F340/F380. However, response to ISO was completely diminished in the presence of calyculin A, an inhibitor of myosin phosphatase. In conclusion, b-adrenergic action antagonizes Ca2+ sensitization mediated by impairment of myosin phosphatase activity. Moreover, cAMP independent process, G protein direct action, is more potent in inhibiting this Ca2+ sensitization than PKA.}, pages = {183--191}, title = {Involvement of reduced sensitivity to Ca2+ in b-adrenergic action on airway smooth muscle}, volume = {36}, year = {2006} }