Article date: July 1997
By: Christina M Pabelick, Kai Rehder, Keith A Jones, Robin Shumway, Sten G E Lindahl, David O Warner, in Volume 121, Issue 7, pages 1378-1382
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.
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.
In strips stimulated with 0.1 μM ACh (EC50) R(−)‐ketamine (1–100 μM) caused a significantly greater concentration‐dependent decrease in force (P<0.0001) and [Ca2+]i than S(+)‐ketamine (1–100 μM) (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 KCl (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).
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.
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.
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.
In strips stimulated with 0.1 μM ACh (EC50) R(−)‐ketamine (1–100 μM) caused a significantly greater concentration‐dependent decrease in force (P<0.0001) and [Ca2+]i than S(+)‐ketamine (1–100 μM) (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 KCl (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).
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.
DOI: 10.1038/sj.bjp.0701280
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