{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:47:09Z","timestamp":1789588029734,"version":"build-2803163510"},"reference-count":49,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R56HL155937"],"award-info":[{"award-number":["R56HL155937"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01HL114471-03"],"award-info":[{"award-number":["P01HL114471-03"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"HHS | NIH | National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR0030117"],"award-info":[{"award-number":["UL1TR0030117"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:p>Epinephrine (EPI), an endogenous catecholamine involved in the body\u2019s fight-or-flight responses to stress, activates \u03b1<jats:sub>1<\/jats:sub>-adrenergic receptors (\u03b1<jats:sub>1<\/jats:sub>ARs) expressed on various organs to evoke a wide range of physiological functions, including vasoconstriction. In the smooth muscle of human bronchi, however, the functional role of EPI on \u03b1<jats:sub>1<\/jats:sub>ARs remains controversial. Classically, evidence suggests that EPI promotes bronchodilation by stimulating \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptors (\u03b2<jats:sub>2<\/jats:sub>ARs). Conventionally, the selective \u03b2<jats:sub>2<\/jats:sub>AR agonism of EPI was thought to be, in part, due to a predominance of \u03b2<jats:sub>2<\/jats:sub>ARs and\/or a sparse, or lack of \u03b1<jats:sub>1<\/jats:sub>AR activity in human airway smooth muscle (HASM) cells. Surprisingly, we find that HASM cells express a high abundance of ADRA1B (the \u03b1<jats:sub>1<\/jats:sub>AR subtype B) and identify a spontaneous \u201cswitch-like\u201d activation of \u03b1<jats:sub>1<\/jats:sub>ARs that evokes intracellular calcium, myosin light chain phosphorylation, and HASM cell shortening. The switch-like responses, and related EPI-induced biochemical and mechanical signals, emerged upon pharmacological inhibition of \u03b2<jats:sub>2<\/jats:sub>ARs and\/or under experimental conditions that induce \u03b2<jats:sub>2<\/jats:sub>AR tachyphylaxis. EPI-induced procontractile effects were abrogated by an \u03b1<jats:sub>1<\/jats:sub>AR antagonist, doxazosin mesylate (DM). These data collectively uncover a previously unrecognized feed-forward mechanism driving bronchospasm via two distinct classes of G protein-coupled receptors (GPCRs) and provide a basis for reexamining \u03b1<jats:sub>1<\/jats:sub>AR inhibition for the management of stress\/exercise-induced asthma and\/or \u03b2<jats:sub>2<\/jats:sub>-agonist insensitivity in patients with difficult-to-control, disease subtypes.<\/jats:p>","DOI":"10.1152\/ajplung.00444.2021","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T12:01:15Z","timestamp":1657022475000},"page":"L142-L151","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Epinephrine evokes shortening of human airway smooth muscle cells following \u03b2<sub>2<\/sub>adrenergic receptor 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