{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:02:52Z","timestamp":1774620172507,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We examined the reduced responsiveness to \u03b2 -adrenergic receptor agonists ( \u03b2 -agonists) after exposure to \u03b2 -agonists, and the mechanisms underlying this phenomenon in isolated human tracheal smooth muscle, using isometric tension records to test the hypothesis that repeated inhalation of \u03b2 -agonists leads to reduced responsiveness to \u03b2 -agonists. The inhibitory effects of isoproterenol (ISO) on contraction by spasmogens participating in asthma attacks diminished markedly after continuous exposure to ISO (0.0003 to 3 \u03bc M) for 45 min; moreover, when ISO was repeatedly applied for 10 min to tissues precontracted by methacholine every 30 min, the relaxant effects of ISO gradually attenuated after these repeated applications. In contrast, reduced \u03b2 -adrenergic relaxation after continuous and repeated exposure to agonists did not occur when tissues were preincubated with 2 \u03bc g\/ ml cholera toxin (CTX), which irreversibly activates guanosine triphosphate (GTP)-binding protein (Gs) coupled with \u03b2 -adrenergic receptors, for 6 h. However, the CTX inhibition disappeared in the presence of iberiotoxin, a selective inhibitor of large conductance Ca2 +-activated K+ (KCa) channels. Our results demonstrate that continuous and repeated exposure to \u03b2 -agonists leads to \u03b2 -adrenergic desensitization, and that activation of KCa channels by Gs prevents this desensitization.<\/jats:p>","DOI":"10.1164\/ajrccm.159.2.9801006","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:53:04Z","timestamp":1365083584000},"page":"452-460","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of \u03b2 -Adrenergic Desensitization by KCa Channels in Human Trachealis"],"prefix":"10.1093","volume":"159","author":[{"given":"HIROAKI","family":"KUME","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, School of Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"KENZO","family":"TAKAGI","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, School of Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1999,2,1]]},"reference":[{"key":"2026032708563000000_B1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/0140-6736(90)93098-A","article-title":"Regular inhaled beta-agonist treatment in bronchial asthma.","volume":"336","author":"Sears","year":"1990","journal-title":"Lancet"},{"key":"2026032708563000000_B2","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S0091-6749(05)80185-X","article-title":"Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol.","volume":"86","author":"van Schayck","year":"1990","journal-title":"J. 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