Effects of ketamine on neostigmine-induced contractile and phosphatidylinositol responses of the rat trachea.
OBJECTIVE
Neostigmine causes airway smooth muscle contraction through the direct stimulation of muscarinic receptors and the activation of phosphatidylinositol (PI) responses. Ketamine attenuates airway smooth muscle contraction. It is not clear whether ketamine attenuates neostigmine-induced airway smooth muscle contraction by inhibiting the PI response. This study was designed to examine the effects of ketamine on neostigmine-induced contractile and PI responses of the rat trachea.


METHODS
Thirty male Wistar rats weighing 250-350 g were used. In the experiment on the contractile response, active contraction was induced with 1 microM neostigmine in the presence or absence of ketamine. In the experiment on the phosphatidylinositol response, the trachea slices were incubated with [3H]myo-inositol, 1 microM neostigmine, or 100 microM aluminum fluoride, and ketamine. The formation of [3H]inositol monophosphate (IP1), a degradation product of the phosphatidylinositol response, was measured with a liquid scintillation counter. Statistical significance (P < 0.05) was determined by analysis of variance.


RESULTS
Neostigmine 1 microM caused tracheal ring contraction. This contraction was attenuated by ketamine dose-dependently and reached resting tension at 100 microM. Neostigmine- and aluminum fluoride-induced IP1, accumulation was also attenuated by ketamine.


CONCLUSIONS
The results suggest that ketamine attenuates neostigmine-induced contractile responses, at least in part, through the inhibition of phospholipase C coupled with G protein in the PI response.
Saito
Masataka
M
Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Shibata
Osamu
O
Yamaguchi
Masakazu
M
Miyoshi
Hiroshi
H
Makita
Tetsuji
T
Sumikawa
Koji
K
D017607:Aluminum Compounds / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000494:pharmacology; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000378:metabolism / Q000502:physiology*
D017607:Aluminum Compounds; D018686:Anesthetics, Intravenous; D002800:Cholinesterase Inhibitors; D010716:Phosphatidylinositols; D009388:Neostigmine; D007649:Ketamine; D005459:Fluorides; C032311:aluminum fluoride