Phosphatidylinositol responses are involved in the vascular effects of thiamylal and fentanyl.
Although thiobarbiturates potentiate, and fentanyl attenuates peripheral vasoconstriction, the intracellular mechanism involved in this phenomenon is not clear. Because smooth muscle contraction induced by alpha 1-adrenoceptor agonists is mediated by the phosphatidylinositol (PI) response, this study was carried out to clarify if thiamylal and fentanyl affect the norepinephrine-induced PI response in rat aortic slices. Rat aortic slices were incubated in Krebs-Henseleit solution containing 5 mM LiCl, [3H]myo-inositol, and varying concentrations of thiamylal or fentanyl. The Pl response was stimulated by 0.9 microM (ED50) norepinephrine (NE). The [3H]inositol monophosphate (IP1) was separated from [3H]myo-inositol by column chromatography and counted with a liquid scintillation counter. The basal IP1 accumulation was not affected by thiamylal and fentanyl. Norepinephrine-induced IP1 accumulation was potentiated by thiamylal at concentrations of 10 microM and 100 microM. Norepinephrine-induced IP1 accumulation was attenuated by 1 microM and 10 microM fentanyl. The results suggest that thiamylal stimulates the NE-induced PI response, which potentiates the vasoconstriction, and fentanyl attenuates NE-induced PI response, which would attenuate the vasoconstriction.
Shibata
O
O
Department of Anesthesiology, Nagasaki University School of Medicine, Japan.
Todoroki
S
S
Terao
Y
Y
Goto
S
S
Hirano
M
M
Fujigaki
T
T
Sumikawa
K
K
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005283:Fentanyl / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013840:Thiamylal / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D010716:Phosphatidylinositols; D013840:Thiamylal; D005283:Fentanyl; D009638:Norepinephrine