Epinephrine evokes shortening of human airway smooth muscle cells following b2 adrenergic receptor desensitization

Brian T. Deeney, Gaoyuan Cao, Sarah Orfanos, Jordan Lee, Mengyuan Kan, Blanca E. Himes, Vishal Parikh, Cynthia J. Koziol-White, Steven An, Reynold A. Panettieri

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Epinephrine (EPI), an endogenous catecholamine involved in the body’s fight-or-flight responses to stress, activates a1-adrenergic receptors (a1ARs) 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 a1ARs remains controversial. Classically, evidence suggests that EPI promotes bronchodilation by stimulating b2-adrenergic receptors (b2ARs). Conventionally, the selective b2AR agonism of EPI was thought to be, in part, due to a predominance of b2ARs and/or a sparse, or lack of a1AR activity in human airway smooth muscle (HASM) cells. Surprisingly, we find that HASM cells express a high abundance of ADRA1B (the a1AR subtype B) and identify a spontaneous “switch-like” activation of a1ARs 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 b2ARs and/or under experimental conditions that induce b2AR tachyphylaxis. EPI-induced procontractile effects were abrogated by an a1AR 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 a1AR inhibition for the management of stress/exercise-induced asthma and/or b2-agonist insensitivity in patients with difficult-to-control, disease subtypes.

Original languageEnglish (US)
Pages (from-to)L142-L151
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2
StatePublished - Aug 2022

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


Dive into the research topics of 'Epinephrine evokes shortening of human airway smooth muscle cells following b2 adrenergic receptor desensitization'. Together they form a unique fingerprint.

Cite this