Role of lysophosphatidylcholine in the desensitization of beta-adrenergic receptors by Ca(2+) sensitization in tracheal smooth muscle.

Abstract

Lysophosphatidylcholine (Lyso-PC) is generally considered to promote tissue inflammation. To determine the involvement of exogenous Lyso-PC in the beta-adrenergic desensitization by phospholipase A2, we examined the inhibitory effects of isoproterenol (ISO) on tension and intracellular Ca(2+) concentration by methacholine (MCh) after continuous exposure to Lyso-PC in guinea-pig tracheal smooth muscle, using isometric tension recordings and fura-2 signal (F340/F380 ratio). Pre- exposure to 10 microM Lyso-PC markedly reduced subsequent inhibition by 0.3 microM ISO against 1 microM MCh-induced contraction in a time-dependent manner. In contrast, values of percent F340/F380 ratio for MCh with ISO were not affected after exposure to Lyso-PC. In the presence of Y-27632, a selective rho-kinase inhibitor, a reduction in subsequent relaxation by ISO after exposure to Lyso-PC was inhibited in a concentration-dependent manner. Preincubation with cholera toxin also inhibited reduced responsiveness to ISO by Lyso-PC. Pre-exposure to Lyso-PC did not attenuate subsequent relaxation by agents that bypass beta-adrenergic receptors. These results indicate that continuous exposure to Lyso-PC may cause homologous desensitization of beta-adrenergic receptors via an augmentation in sensitivity to Ca(2+) by rho, a small G protein, in airway smooth muscle, and that activation of the stimulatory G protein of adenylyl cyclase, G(s), may prevent this phenomenon.

• Authors: H Kume, S Ito, Y Ito, K Yamaki
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 25 Issue 3 Pg. 291-8 (Sep 2001) ISSN: 1044-1549 [Print] United States
• PMID: 11588006 (Publication Type: Journal Article)

Chemical References

• Adenylate Cyclase Toxin
• Adrenergic beta-Agonists
• Amides
• Enzyme Inhibitors
• Indoles
• Lysophosphatidylcholines
• Maleimides
• Muscarinic Agonists
• Pyridines
• Receptors, Adrenergic, beta
• Virulence Factors, Bordetella
• Methacholine Chloride
• Y 27632
• Colforsin
• Bucladesine
• Cholera Toxin
• Theophylline
• rho GTP-Binding Proteins
• Dinoprostone
• Isoproterenol
• bisindolylmaleimide
• Calcium

Topics

• Adenylate Cyclase Toxin
• Adrenergic beta-Agonists (pharmacology)
• Amides (pharmacology)
• Animals
• Bucladesine (pharmacology)
• Calcium (metabolism)
• Cholera Toxin (pharmacology)
• Colforsin (pharmacology)
• Dinoprostone (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Guinea Pigs
• In Vitro Techniques
• Indoles (pharmacology)
• Isoproterenol (pharmacology)
• Lysophosphatidylcholines (pharmacology)
• Male
• Maleimides (pharmacology)
• Methacholine Chloride (pharmacology)
• Muscarinic Agonists (pharmacology)
• Muscle Contraction (physiology)
• Muscle, Smooth (drug effects, metabolism)
• Pyridines (pharmacology)
• Receptors, Adrenergic, beta (metabolism)
• Spectrometry, Fluorescence
• Theophylline (pharmacology)
• Trachea (drug effects, metabolism)
• Virulence Factors, Bordetella (pharmacology)
• rho GTP-Binding Proteins (metabolism)