| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
2 Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6; and 1 Howard Hughes Medical Institute, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710
Contraction and relaxation of airway
smooth muscles is mediated, in part, by G protein-coupled receptors
(GPCRs) and dysfunction of these receptors has been implicated in
asthma. Phosphorylation of GPCRs, by G protein-coupled receptor kinase
(GRK), is an important mechanism involved in the dampening of GPCR
signaling. To determine whether this mechanism might play a role in
airway smooth muscle physiology, we examined the airway pressure time
index and heart rate (HR) responses to intravenous administration of
the cholinergic agonist methacholine (MCh) in genetically altered mice
lacking one copy of GRK2 (GRK2 +/
), homozygous GRK3 knockout
(GRK3 /), and wild-type littermates. (GRK2
/ mice die in utero.) GRK3 / mice
demonstrated a significant enhancement in the airway response to 100 and 250 µg/kg doses of MCh compared with wild-type and GRK2 +/
mice. GRK3 / mice also displayed an enhanced sensitivity of the airway smooth muscle response to MCh. In addition, GRK3 / mice displayed an altered HR recovery from MCh-induced
bradycardia. Although direct stimulation of cardiac muscarinic
receptors measured as vagal stimulation-induced bradycardia was similar
in GRK3 / and wild-type mice, the baroreflex increase in
HR associated with sodium nitroprusside-induced hypotension was
significantly greater in GRK3 / than wild-type mice.
Therefore, these data demonstrate that in the mouse, GRK3 may be
involved in modulating the cholinergic response of airway smooth muscle
and in regulating the chronotropic component of the baroreceptor reflex.
transgenic mice; methacholine; cardiac baroreflex; bronchial hyperreactivity; airway responsiveness; asthma
This article has been cited by other articles:
|
|
 |
|
  D. A. Deshpande, B. S. Theriot, R. B. Penn, and J. K. L. Walker {beta}-Arrestins specifically constrain {beta}2-adrenergic receptor signaling and function in airway smooth muscle FASEB J, July 1, 2008; 22(7): 2134 - 2141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Brass, J. W. Hollingsworth, E. McElvania-Tekippe, S. Garantziotis, I. Hossain, and D. A. Schwartz CD14 is an essential mediator of LPS-induced airway disease Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L77 - L83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. L. Walker, R. R. Gainetdinov, D. S. Feldman, P. K. McFawn, M. G. Caron, R. J. Lefkowitz, R. T. Premont, and J. T. Fisher G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L312 - L319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Hardouin, K. N. Richmond, A. Zimmerman, S. E. Hamilton, E. O. Feigl, and N. M. Nathanson Altered Cardiovascular Responses in Mice Lacking the M1 Muscarinic Acetylcholine Receptor J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 129 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Volgyesi, L. N. Tremblay, P. Webster, N. Zamel, and A. S. Slutsky A new ventilator for monitoring lung mechanics in small animals J Appl Physiol, August 1, 2000; 89(2): 413 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Bohn, R. J. Lefkowitz, R. R. Gainetdinov, K. Peppel, M. G. Caron, and F. Lin Enhanced Morphine Analgesia in Mice Lacking -Arrestin 2 Science, December 24, 1999; 286(5449): 2495 - 2498. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
