Effects of Intravenous Anesthetics on Phosphatidylinositol Turnover in Rat Cerebral Cortical Prisms

Abstract

Noradrenergic pathways in the brain have been thought to be related to the site of anesthetic action. Norepinephrine (NE) in the central nervous system stimulates phosphatidylinositol (PI) turnover through alpha 1-adrenergic receptors. The present study was designed to examine the effects of intravenous anesthetics on NE-induced PI turnover in rat cerebral cortical prisms. NE-induced inositol monophosphate (IP1) formation was inhibited by droperidol (dose for 50% inhibition [ID50], 0.0258 +/- 0.00023 microM [mean +/- SE]), fentanyl (2.36 +/- 0.0017), diazepam (201 +/- 2.12), and thiamylal (231 +/- 1.94) in a dose-dependent manner, but was not affected by ketamine. Naloxone or flumazenil did not attenuate the inhibitory effect of fentanyl or diazepam on NE-induced IP1 formation. The results suggest that these effects on the PI turnover in the cortex may be related to their pharmacologic properties including the anesthetic action.

Phosphatidylinositol responses are involved in the vascular effects of thiamylal and fentanyl

“…White et al 6 found, in dogs, that pretreatment with naloxone did not alter the vascular response to fentanyl. Makita et al 24 reported that naloxone did not affect the inhibitory effect of fentanyl on the NE-induced PI response in rat cerebral cortical prisms. Thus, attenuation of the PI response by fentanyl would not be mediated by opioid receptors.…”

2 Receptor mechanisms and their role in drug interactions: effects of anaesthetics on G-protein-activated intracellular signalling pathways

“…There are limited data on the effects of other intravenous anaesthetics on InsP3 signalling. Fentanyl (MaNta et al, 1994;Shibata et al, 1995) and diazepam (Makita et al, 1994) inhibit noradrenaline-induced InsP1 formation in rat aorta and/or cortex, but were without effect in rat liver (Shibata et al, 1993). The barbiturates thiopentone (Shibata et al, 1995) and thiamylal (Shibata et al, 1993) were reported to stimulate noradrenaline-mediated InsP, production.…”