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Anesthesiology. 1997 Jul;87(1):94-101.

Halothane attenuation of calcium sensitivity in airway smooth muscle. Mechanisms of action during muscarinic receptor stimulation.

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  • 1Department of Anesthesiology, Physiology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Abstract

BACKGROUND:

In airway smooth muscle, muscarinic receptor stimulation is thought to increase calcium (Ca2+) sensitivity via a guanosine 5'-triphosphate (GTP)-binding protein/protein kinase C (PKC)-mediated mechanism. This study treated the hypothesis that halothane reduces Ca2+ sensitivity during muscarinic receptor stimulation by inhibiting these second messenger pathways.

METHODS:

A beta-escin permeabilized canine tracheal smooth muscle preparation was used in which the cytosolic Ca2+ concentration ([Ca2+]i) is controlled and the GTP-binding protein/ PKC pathways remain intact and can be activated. The muscarinic receptor was activated with acetylcholine plus GTP; the GTP-binding proteins were directly activated with a nonhydrolyzable form of GTP, guanosine 5'-O-(3-thiotriphosphate; GTP gamma S); and PKC was directly activated with the PKC agonist phorbol 12,13-dibutyrate (PDBu).

RESULTS:

Free Ca2+ caused a concentration-dependent increase in force. Acetylcholine plus GTP significantly decreased the median effective concentration for free Ca2+ from 0.52 +/- 0.06 microM to 0.21 +/- 0.02 microM, demonstrating an increase in Ca2+ sensitivity. Halothane (0.99 +/- 0.04 mM, equivalent to approximately 4 minimum alveolar concentration in dogs) significantly attenuated this increase in Ca2+ sensitivity induced by acetylcholine plus GTP, increasing the median effective concentration for free Ca2+ from 0.21 +/- 0.02 microM to 0.31 +/- 0.03 microM. However, halothane did not affect the increases in Ca2+ sensitivity induced by GTP gamma S or PDBu.

CONCLUSIONS:

Halothane had no effect on increased Ca2+ sensitivity caused by direct activation of GTP-binding proteins with GTP gamma S or PKC with PDBu, suggesting that halothane attenuates acetylcholine-induced Ca2+ sensitization via a mechanism independent of these pathways in beta-escin-permeabilized canine tracheal smooth muscle.

PMID:
9232139
[PubMed - indexed for MEDLINE]
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