Allergens, IgE, mediators, inflammatory mechanisms Reduced adenylyl cyclase activation with no decrease in 13-adrenergic receptors in basenji greyhound leukocytes: Relevance to 13-adrenergic responses in airway smooth muscle

Mononuclear leukocytes (MNLs) have been used as a model of [3-adrenergic responsiveness of airway smooth muscle, but the relevance of this model remains controversial. The basenji . greyhound (BG) dog model of airway hyperresponsiveness shares some features with human asthma, and airway smooth muscle shows a selective impairment in isoproterenol-stimulated adenylyl eyclase activity. In this study, MNL membranes were obtained from these same dogs, and the [3-adrenergic receptor-adenylyl cascade function was compared with that in airway smooth muscle. [3-Adrenergic receptor numbers and affinities for iodine 125-cyanopindolol were similar in the two dog groups (receptor numbers [BmoJ = 441 +_ 101 and 447 +_ 61 fmol/mg protein and dissociation constant [Ka] = 269 +- 44 and 312 +_ 60 pmol/L for mongrel and BG MNLs, respectively). Quantities of the Gsa protein were not different in the membranes as determined by immunoblotting. Stimulation of adenylyl cyclase by isoproterenol (100 pmol/L) was impaired in MNL membranes of BG membranes (22% +4% increase over guanosine triphosphate [10 txmol/L]) compared with mongrel membranes (47% + 8.6% increase over guanosine triphosphate [10 lamol/L], p < 0.05). Stimulation of adenylyl cyclase by prostaglandin E~ (10 pmol/L), NaF (10 mmol/L), or forskolin (10 Ixmol/ L) did not differ in membranes from the two groups. No difference was found in the lymphocyte subsets in the two groups as determined by flow cytometry. These findings are qualitatively similar to studies of trachealis muscle membranes from these same dogs. We have found a selective impairment of isoproterenol stimulation of adenylyl cyclase in membranes prepared from MNLs of the BG dog, which was previously found in airway smooth muscle membranes despite no decrease in numbers of [3-adrenergic receptors. (J ALLERGY CLIN IMMUNOL 1995;95:860-7.)