PMID- 16571971
OWN - NLM
STAT- MEDLINE
DCOM- 20060504
LR  - 20191210
IS  - 0003-3022 (Print)
IS  - 0003-3022 (Linking)
VI  - 104
IP  - 4
DP  - 2006 Apr
TI  - Halothane does not inhibit the functional coupling between the beta2-adrenergic 
      receptor and the Galphas heterotrimeric G protein.
PG  - 754-62
AB  - BACKGROUND: This study investigated whether halothane affects the functional 
      coupling between the beta2 adrenergic receptor and the alpha subunit of its 
      cognate stimulatory heterotrimeric guanosine-5'-triphosphate (GTP)-binding 
      protein (Galphas). The authors hypothesized that halothane does not affect 
      isoproterenol-promoted guanosine nucleotide exchange at Galphas and hence would 
      not affect isoproterenol-induced relaxation of airway smooth muscle. METHODS: 
      Halothane effects on isoproterenol-induced inhibition of calcium sensitivity were 
      measured in permeabilized porcine airway smooth muscle. Galphas nucleotide 
      exchange was measured in crude membranes prepared from COS-7 cells transfected to 
      transiently coexpress the human beta1 or beta2 receptor each with human short 
      Galphas. A radioactive, nonhydrolyzable analog of GTP, [S]GTPgammaS, was used as 
      the reporter for nucleotide exchange at Galphas. RESULTS: Halothane (0.75 mm, 
      approximately 2.8 minimum alveolar concentration [MAC] in pigs) did not affect 
      isoproterenol-induced inhibition of calcium sensitivity. Isoproterenol caused a 
      time- and concentration-dependent increase in Galphas nucleotide exchange. 
      Halothane, even at concentrations of 1.5 mm (approximately 5.6 MAC), had no 
      effect on basal Galphas nucleotide exchange in the absence of isoproterenol, 
      whereas halothane inhibited isoproterenol-promoted Galphas nucleotide exchange in 
      both the beta1-Galphas and beta2-Galphas expressing membranes. However, the 
      effect was significantly greater on beta1-Galphas coupling compared with 
      beta2-Galphas coupling, with no effect on beta2-Galphas coupling at 2.8 MAC 
      halothane. CONCLUSION: Halothane does not inhibit the biochemical coupling 
      between the beta2 receptor and Galphas and hence does not affect the inhibition 
      of calcium sensitivity induced by isoproterenol. Therefore, halothane should not 
      affect the efficacy of beta2 agonists, as suggested by studies of in vivo animal 
      models of asthma.
FAU - Hayashi, Masao
AU  - Hayashi M
AD  - Department of Anesthesiology, Mayo Foundation, Rochester, Minnesota 55905, USA.
FAU - Penheiter, Sumedha G
AU  - Penheiter SG
FAU - Nakayama, Tetsuzo
AU  - Nakayama T
FAU - Penheiter, Alan R
AU  - Penheiter AR
FAU - Warner, David O
AU  - Warner DO
FAU - Jones, Keith A
AU  - Jones KA
LA  - eng
GR  - HL-45532/HL/NHLBI NIH HHS/United States
GR  - HL-54757/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
RN  - L628TT009W (Isoproterenol)
RN  - SY7Q814VUP (Calcium)
RN  - UQT9G45D1P (Halothane)
SB  - IM
MH  - Anesthetics, Inhalation/*pharmacology
MH  - Animals
MH  - COS Cells
MH  - Calcium/metabolism
MH  - Chlorocebus aethiops
MH  - Dose-Response Relationship, Drug
MH  - GTP-Binding Protein alpha Subunits, Gs/*drug effects/physiology
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
MH  - Guanosine Diphosphate/metabolism
MH  - Halothane/*pharmacology
MH  - Isoproterenol/pharmacology
MH  - Receptors, Adrenergic, beta-2/*drug effects/physiology
MH  - Swine
EDAT- 2006/03/31 09:00
MHDA- 2006/05/05 09:00
CRDT- 2006/03/31 09:00
PHST- 2006/03/31 09:00 [pubmed]
PHST- 2006/05/05 09:00 [medline]
PHST- 2006/03/31 09:00 [entrez]
AID - 00000542-200604000-00020 [pii]
AID - 10.1097/00000542-200604000-00020 [doi]
PST - ppublish
SO  - Anesthesiology. 2006 Apr;104(4):754-62. doi: 10.1097/00000542-200604000-00020.