Inhibition of brain adenylate cyclase by barbiturates through the effect on the interaction between guanine nucleotide-binding stimulatory regulatory protein and catalitic unit.

Anesthetic Barbiturates Enhance Gsα‐Dependent Cyclic AMP Production in S49 Mouse Lymphoma Cells

“…The effect of pentobarbital may not be present in these preparations because either a necessary aspect of membrane architecture is lost when the cells are disrupted, or cytosolic components are required, and they are removed from the membrane preparations or diluted in the homogenized preparations. The apparent discrepancy between the results in the current study and those of others (Dan'ura et al ., , 1987(Dan'ura et al ., , 1989) may be due to the use of a different cell type, the use of different drugs to activate adenylyl cyclase, or the use of lower concentrations of pentobarbital .…”

“…Although we have shown that pentobarbital enhances cAMP accumulation in unstimulated (basal) and agonist-stimulated WT cells, others have reported that pentobarbital, at concentrations up to 5 mM, decreases GppNHp-, NaF-AIC13-, and forskolin-stimulated adenylyl cyclase activity in membranes prepared from rat brain (Dan'ura et al, , 1987(Dan'ura et al, , 1989 . We, therefore, investigated the effects of pentobarbital on cAMP accumulation in broken-cell preparations from WT cells.…”

“…Volatile anesthetics disrupt muscarinic receptor-G protein coupling (Anthony et al ., 1989 ;Aronstam and Dennison, 1989), and barbiturates inhibit inositol phospholipid hydrolysis through an interaction with a G protein (Robinson-White et al ., 1989, 1990 . Barbiturates also affect the regulation of adenylyl cyclase in preparations of membranes from rat brain (Dan'ura et al ., , 1987(Dan'ura et al ., , 1989 . Barbiturates were found to inhibit adenylyl cyclase that was stimulated by 5'-guanylylimidodiphosphate (GppNHp), NaF-AIC1 3 , or forskolin .…”

“…Forskolin, a naturally occurring diterpine, stimulates adenylyl cyclase both by activating directly the catalytic moiety at a low-affinity binding site and by facilitating interactions between G_ and adenylyl cyclase at a high-affinity binding site (Barber and Goka, 1985 ;Seamon and Daly, 1986 ;Yamashita et al, 1986) . The effects of barbiturates on adenylyl cyclase in membranes prepared from rat brain suggest that these drugs inhibit the interaction of the stimulatory G protein with adenylyl cyclase (Dan'ura et al ., , 1987(Dan'ura et al ., , 1989 . These investigators did not examine the effects of barbiturates on the regulation of CAMP pathways by agonist-occupied receptors, and to date, no studies have examined the effects of barbiturates on the regulation of CAMP pathways in intact cells .…”

Inhibition of Activator Protein 1 by Barbiturates Is Mediated by Differential Effects on Mitogen-Activated Protein Kinases and the Small G Proteins Ras and Rac-1

“…Therefore, we postulate that barbiturates can directly affect small G proteins. Indeed, our data are supported by reports demonstrating altered activity of GTP binding proteins upon phenobarbital treatment in rat brain or in a rat basophilic leukemia cell line (Dan'ura et al, 1987;Robinson-White et al, 1990).…”