PMID- 8308741
OWN - NLM
STAT- MEDLINE
DCOM- 19940314
LR  - 20190512
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 470
DP  - 1993 Oct
TI  - Role of GTP-protein and endothelium in contraction induced by ethanol in pig 
      coronary artery.
PG  - 521-37
AB  - 1. We examined the effects of ethanol on the contractility of strips of porcine 
      coronary artery, with and without endothelium, and following permeabilization 
      with alpha-toxin, and of aortic valvular endothelial cells, in situ. Changes in 
      cytosolic Ca2+ concentration ([Ca2+]i) of the coronary artery smooth muscle cells 
      and of the valvular endothelial cells were monitored using front-surface 
      fluorometry of the calcium indicator dye, fura-2. In permeabilized preparations, 
      [Ca2+]i was clamped using 10 mM 
      ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetra ace tic acid (EGTA) and 
      10 microM A23187 (a calcium ionophore). 2. The strips without endothelium were 
      placed in normal physiological salt solution (normal PSS) in the presence of 
      ethanol (100-1000 mM). There were dose-dependent increases in [Ca2+]i and a rapid 
      sustained rise in tension. In Ca(2+)-free PSS, ethanol increased [Ca2+]i and 
      tension, similar to, but much smaller than, findings with normal PSS. 3. For a 
      given change in [Ca2+]i induced by ethanol, the developed tension was greater 
      than that observed during contractions induced by high [K+]o. Thus, the 
      [Ca2+]-tension curve for ethanol was shifted to the left of that for high [K+]o. 
      The [Ca2+]-tension curve for the contraction induced by ethanol in the absence of 
      extracellular Ca2+ was shifted further to the left from that obtained in the 
      presence of [Ca2+]o. 4. The mechanisms involved in this Ca(2+)-sensitizing effect 
      of ethanol were investigated using alpha-toxin-permeabilized coronary medial 
      strips. Ethanol increased the tension development, in a concentration-dependent 
      manner, at a fixed concentration of Ca2+ (pCa = 6.3) in the presence of 
      guanosine-5'-triphosphate (GTP), an effect antagonized by 
      guanosine-5'-O-(beta-thiodiphosphate) (GDP beta S), a non-hydrolysable GDP 
      analogue. 5. With intact endothelium, the ethanol-induced tension development was 
      markedly reduced, although inhibition in the increase in [Ca2+]i was slight. The 
      [Ca2+]-tension relationship of this contraction overlapped with that obtained 
      with high [K+]o-induced contraction and was shifted to the right from that 
      obtained in the absence of the endothelium. This endothelium-dependent reduction 
      of [Ca2+]i and tension induced by ethanol was inhibited when the strips were 
      exposed to NG-monomethyl-L-arginine (L-NMMA). 6. Ethanol induced a gradual and 
      sustained increase in [Ca2+]i in normal PSS, and a transient, 
      concentration-dependent increase in [Ca2+]i in Ca(2+)-free PSS in porcine aortic 
      valvular endothelial cells in situ.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Kuroiwa, M
AU  - Kuroiwa M
AD  - Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, 
      Fukuoka, Japan.
FAU - Aoki, H
AU  - Aoki H
FAU - Kobayashi, S
AU  - Kobayashi S
FAU - Nishimura, J
AU  - Nishimura J
FAU - Kanaide, H
AU  - Kanaide H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3K9958V90M (Ethanol)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - Animals
MH  - Biotransformation/drug effects
MH  - Calcium/pharmacology
MH  - Cell Membrane Permeability/drug effects
MH  - Coronary Vessels/drug effects
MH  - Endothelium, Vascular/*physiology
MH  - Ethanol/*pharmacology
MH  - Fluorometry
MH  - Fura-2
MH  - GTP-Binding Proteins/metabolism/*physiology
MH  - In Vitro Techniques
MH  - Muscle Contraction/drug effects
MH  - Muscle, Smooth, Vascular/drug effects/*physiology
MH  - Nitric Oxide/metabolism
MH  - Swine
MH  - Temperature
PMC - PMC1143932
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
PMCR- 1993/10/01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
PHST- 1993/10/01 00:00 [pmc-release]
AID - 10.1113/jphysiol.1993.sp019873 [doi]
PST - ppublish
SO  - J Physiol. 1993 Oct;470:521-37. doi: 10.1113/jphysiol.1993.sp019873.