title: Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Pabelick
authors.forename: K
authors.initials: K
authors.lastname: Rehder
authors.forename: K A
authors.initials: KA
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Shumway
authors.forename: S G
authors.initials: SG
authors.lastname: Lindahl
authors.forename: D O
authors.initials: DO
authors.lastname: Warner
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008345:Manganese / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D001993:Bronchodilator Agents; D008345:Manganese; D007649:Ketamine; D000109:Acetylcholine