These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Halothane attenuation of calcium sensitivity in airway smooth muscle. Mechanisms of action during muscarinic receptor stimulation.
    Author: Bremerich DH, Hirasaki A, Jones KA, Warner DO.
    Journal: Anesthesiology; 1997 Jul; 87(1):94-101. PubMed ID: 9232139.
    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.
    [Abstract] [Full Text] [Related] [New Search]