Bypassing β2 adrenergic receptor in isoproterenol desensitized airway smooth muscle with forskolin

CHED 1352

Jennifer Hill, hil39500@obu.edu1, Crystal Pate, hil39500@obu.edu2, Stacie M. Jones2, and Richard C. Kurten, hil39500@obu.edu3. (1) Department of Chemistry, Ouachita Baptist University, 410 Ouachita Street, Arkadelphia, AR 71998, (2) Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Hospital Children's Hospital Research Institute, Little Rock, AR 72205, (3) Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Arkansas Hospital Children's Hospital Research Institute, Little Rock, AR 72205
A primary feature of asthma is bronchial constriction due to smooth muscle hyperactivity. β-agonists are mainstay treatments for asthma, but the use of this class of dugs is compromised by the issue of tolerance. This study used a rat lung model to determine if tolerance occurs prior to or after the activation of adenylyl cyclase by β-agonists. The ability of isoproterenol (ISO) to relax methacholine (MCh) pre-contracted bronchioles declined with repetitive dosing. Forskolin (FSK), a pharmacological activator of adenylyl cyclase, attenuated contraction in response to MCh. In addition, FSK relaxed pre-contracted bronchioles exhibiting tolerance to β-agonists. Therefore, tolerance to isoproterenol involves a step prior to the generation of cAMP. FSK's effect was greater for pre-contracted bronchioles than for relaxed bronchioles. These results indicate that the pathway for relaxation downstream of adenylyl cyclase remains intact after the induction of tolerance to a β-agonist, defining an area for focus in human therapies.
 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007