Linked Life Data

14565944

Source:http://linkedlifedata.com/resource/pubmed/id/14565944

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-8
pubmed:abstractText
G protein-coupled receptors (GPCRs) transduce extracellular signals into intracellular events. The waning responsiveness of GPCRs in the face of persistent agonist stimulation, or desensitization, is a necessary event that ensures physiological homeostasis. GPCR kinases (GRKs) are important regulators of GPCR desensitization. GRK5, one member of the GRK family, desensitizes central M(2) muscarinic receptors in mice. We questioned whether GRK5 might also be an important regulator of peripheral muscarinic receptor responsiveness in the cardiopulmonary system. Specifically, we wanted to determine the role of GRK5 in regulating muscarinic receptor-mediated control of airway smooth muscle tone or regulation of cholinergic-induced bradycardia. Tracheal pressure, heart rate, and tracheal smooth muscle tension were measured in mice having a targeted deletion of the GRK5 gene (GRK5(-/-)) and littermate wild-type (WT) control mice. Both in vivo and in vitro results showed that the airway contractile response to a muscarinic receptor agonist was not different between GRK5(-/-) and WT mice. However, the relaxation component of bilateral vagal stimulation and the airway smooth muscle relaxation resulting from beta(2)-adrenergic receptor activation were diminished in GRK5(-/-) mice. These data suggest that M(2) muscarinic receptor-mediated opposition of airway smooth muscle relaxation is regulated by GRK5 and is, therefore, excessive in GRK5(-/-) mice. In addition, this study shows that GRK5 regulates pulmonary responses in a tissue- and receptor-specific manner but does not regulate peripheral cardiac muscarinic receptors. GRK5 regulation of airway responses may have implications in obstructive airway diseases such as asthma or chronic obstructive pulmonary disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L312-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14565944-Animals, pubmed-meshheading:14565944-Bronchodilator Agents, pubmed-meshheading:14565944-Carbachol, pubmed-meshheading:14565944-Cholinergic Agonists, pubmed-meshheading:14565944-Electric Stimulation, pubmed-meshheading:14565944-G-Protein-Coupled Receptor Kinase 5, pubmed-meshheading:14565944-Gene Expression, pubmed-meshheading:14565944-Heart Rate, pubmed-meshheading:14565944-Isoproterenol, pubmed-meshheading:14565944-Mice, pubmed-meshheading:14565944-Mice, Inbred C57BL, pubmed-meshheading:14565944-Mice, Transgenic, pubmed-meshheading:14565944-Muscle, Smooth, pubmed-meshheading:14565944-Muscle Contraction, pubmed-meshheading:14565944-Parasympathetic Nervous System, pubmed-meshheading:14565944-Protein-Serine-Threonine Kinases, pubmed-meshheading:14565944-Receptor, Muscarinic M2, pubmed-meshheading:14565944-Receptor, Muscarinic M3, pubmed-meshheading:14565944-Trachea, pubmed-meshheading:14565944-Vagus Nerve
pubmed:year
2004
pubmed:articleTitle
G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation.
pubmed:affiliation
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. walke082@mc.duke.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't