PMID- 9232139
OWN - NLM
STAT- MEDLINE
DCOM- 19970821
LR  - 20190628
IS  - 0003-3022 (Print)
IS  - 0003-3022 (Linking)
VI  - 87
IP  - 1
DP  - 1997 Jul
TI  - Halothane attenuation of calcium sensitivity in airway smooth muscle. Mechanisms 
      of action during muscarinic receptor stimulation.
PG  - 94-101
AB  - 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.
FAU - Bremerich, D H
AU  - Bremerich DH
AD  - Department of Anesthesiology, Physiology, Mayo Clinic, Rochester, Minnesota 
      55905, USA.
FAU - Hirasaki, A
AU  - Hirasaki A
FAU - Jones, K A
AU  - Jones KA
FAU - Warner, D O
AU  - Warner DO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Receptors, Muscarinic)
RN  - SY7Q814VUP (Calcium)
RN  - UQT9G45D1P (Halothane)
SB  - IM
MH  - Anesthetics, Inhalation/*pharmacology
MH  - Animals
MH  - Calcium/*physiology
MH  - Dogs
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Halothane/*pharmacology
MH  - Male
MH  - Muscarinic Agonists/pharmacology
MH  - Muscle, Smooth/*drug effects/physiology
MH  - Receptors, Muscarinic/*physiology
MH  - Respiratory Physiological Phenomena
MH  - Respiratory System/*drug effects
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - 10.1097/00000542-199707000-00013 [doi]
PST - ppublish
SO  - Anesthesiology. 1997 Jul;87(1):94-101. doi: 10.1097/00000542-199707000-00013.