Treatment of bronchoconstriction in asthma relies on the use of β-adrenergic receptor agonists that stimulate cAMP production in bronchial smooth muscle cells, inducing bronchodilation. The different isoforms of adenylyl cyclase (AC) that produce cAMP have distinctively different properties, but the effects these features have on cell physiology are poorly understood. Bogard et al. sought to characterize the localization of these proteins in membrane microdomains and to define the regulation of their activities by key receptors in human bronchial smooth muscle cells (hBSMC). hBSMCs were shown to express primarily the isoforms AC2, AC4, and AC6. AC6 colocalizes with at least a portion of the cell's β-adrenergic receptors on caveolin-rich lipid rafts. AC2 and AC4 colocalize with and couple to prostaglandin E2 receptors in the non–lipid-raft membrane fractions of hBSMCs. These results highlight how cellular responses to hormones or neurotransmitters such as catecholamines and prostaglandins can be significantly influenced by the AC isoform expressed in cells. Therefore, it may be particularly important to understand AC isoform expression and localization in airway smooth muscle from patients with asthma or chronic obstructive pulmonary disease.
See article at J Pharmacol Exp Ther 2011, 337:209–217.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics