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1. Ketamine is a potent bronchodilator which relaxes airway smooth muscle (ASM). Clinically, ketamine is used as a 1:1 racemic mixture of enantiomers that differ in their analgesic and anaesthetic effects. The aim of this study was to determine whether there was a difference between the enantiomers in their ability to relax isolated ASM and to explore mechanisms responsible for any observed differences. 2. Canine tracheal smooth muscle strips were loaded with fura-2 and mounted in a photometric system to measure simultaneously force and [Ca2+]i. Calcium influx was estimated by use of a manganese quenching technique. 3. In strips stimulated with 0.1 microM ACh (EC50) R(-)-ketamine (1-100 microM) caused a significantly greater concentration-dependent decrease in force (P<0.0001) and [Ca2+]i than S(+)-ketamine (1-100 microM) (P<0.0005). In contrast, there was no significant difference between the enantiomers in their ability to inhibit calcium influx (45% decrease in influx rate for R(-)-ketamine and 44% for S(+)-ketamine, P =0.782). In strips contracted with 24 mM isotonic KCI (which activates voltage-operated calcium channels), the enantiomers modestly decreased force and [Ca2+]i; there was no significant difference between the enantiomers in their effects on force (P=0.425) or [Ca2+]i (P=0.604). 4. The R(-)-enantiomer of ketamine is a more potent relaxant of ACh-induced ASM contraction than the S(+)-enantiomer. This difference appears to be caused by differential actions on receptor-operated calcium channels.
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
August 1986,
Journal of applied physiology (Bethesda, Md. : 1985),
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
June 1987,
Archives internationales de pharmacodynamie et de therapie,
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
May 1974,
British journal of anaesthesia,
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
April 1990,
Japanese journal of pharmacology,
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
January 2000,
Anesthesiology,
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
August 1988,
The Journal of pharmacology and experimental therapeutics,
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
May 1981,
Pflugers Archiv : European journal of physiology,
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
January 2001,
Journal of applied physiology (Bethesda, Md. : 1985),
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
June 1999,
Anesthesia and analgesia,
C M Pabelick, and
K Rehder, and
K A Jones, and
R Shumway, and
S G Lindahl, and
D O Warner
July 1998,
The European respiratory journal,
