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 α1-adrenoceptor agonists is mediated by the phosphatidylinositol (PI) response, this study was carried out to clarify if thiamylal and fentanyl affect the norepinephrineinduced 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 PI response was stimulated by 0.09 μM (ED50) norepinephrine (NE). The [3H]inositoI 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 μM and 100 μM. Norepinephrine-induced IP1 accumulation was attentuated by 1 μM and 10 μM fentanyl. The results suggest that thiamylal stimulates the NE-induced PI response, which potentiates the vasoconstriction, and fentanyl attentuates NE-induced PI response, which would attenuate the vasoconstriction.