Effective inhibition by pentobarbital of forskolin-stimulated adenylate cyclase activity in rat brain.

Dan'ura, Toshio; Kurokáwa, Tomonori; Yamashita, Atsushi; Ishibashi, Shun

doi:10.1248/cpb.37.3142

Cited by 7 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Discussioncontrasting

confidence: 54%

“…There was, however, no apparent effect on the Gi-regulated pathway . The effect on WT cells occurred at pentobarbital concentrations comparable to those required to inhibit G protein-regulated phospholipid hydrolysis in vitro (Robinson-White et al, 1989, 1990 and at concentrations lower than those required to inhibit G proteindependent adenylyl cyclase activity in membranes prepared from rat brain (Dan'ura et al, , 1987(Dan'ura et al, , 1989 . Thus, considering the results of the current study and the results of others, it appears that barbiturates have effects on several G protein-regulated pathways, but this effect is not generalized to all G proteinregulated pathways.…”

Section: Discussionmentioning

confidence: 92%

“…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 .…”

Section: Discussionmentioning

confidence: 99%

“…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 .…”

mentioning

confidence: 99%

“…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 .…”

mentioning

confidence: 99%

See 4 more Smart Citations

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

Gonzales

1995

Journal of Neurochemistry

View full text Add to dashboard Cite

Cyclic AMP (cAMP) regulates many important physiological processes. Barbiturates influence cAMP regulation, possibly through effects on G proteins. This study used intact S49 mouse lymphoma cells to characterize the role of G proteins in the effect of barbiturates on cAMP regulation. cAMP accumulation was determined in intact S49 WT (wild‐type) and S49 cyc− cells (the Gsα‐deficient mutant) by measuring the conversion of [3H]‐ATP to [3H]cAMP in cells preloaded with [3H]adenine. Pentobarbital enhanced cAMP accumulation in WT cells in the absence (basal) or presence of isoproterenol but had no effect on the EC50 for isoproterenol. This effect was dose dependent with a 50–60% enhancement at 2 mM pentobarbital. Pentobarbital did not affect forskolin‐stimulated cAMP accumulation in WT cells. In cyc− cells, basal and forskolin‐stimulated cAMP accumulation were stimulated only at the highest concentration of pentobarbital used (2 mM). Pentobarbital did not affect the inhibition of cAMP accumulation by somatostatin in WT cells, and pertussis toxin treatment of WT cells did not affect the action of pentobarbital on cAMP accumulation. Pentobarbital did not affect isoproterenol‐stimulated adenylyl cyclase activity in whole‐cell homogenates or membranes prepared from WT cells. The S‐(−)‐isomer of pentobarbital enhanced isoproterenol‐stimulated cAMP accumulation more than the R‐(+)‐isomer. Phenobarbital and barbituric acid did not enhance isoproterenol‐stimulated cAMP accumulation, whereas the anesthetic barbiturates hexobarbital, pentobarbital, and thiopental all enhanced activity. These results suggest that pentobarbital enhances cAMP accumulation in intact WT cells by a mechanism that is dependent on Gsα but independent of Gi. The properties of barbiturates that are responsible for the enhancement of cAMP accumulation may be related to the properties that are responsible for producing sedation and anesthesia.

show abstract

Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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

Gonzales

1995

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

Chronic pentobarbital administration alters ?-aminobutyric acidA receptor ?6-subunit mRNA levels and diazepam-insensitive [3H]Ro15-4513 binding

Ito

Suzuki

Wellman

et al. 1996

Synapse

View full text Add to dashboard Cite

In order to study the chronic effects of pentobarbital, a positive GABAA receptor modulator, on the inverse agonist binding of the benzodiazepine site, binding of [3H]Ro15‐4513 and levels of GABAA receptor α6‐subunit mRNA were investigated in the brains of pentobarbital‐tolerant/dependent animals, using receptor autoradiography and in situ hybridization histochemistry in consecutive brain sections. Pentobarbital was administered to rats either 60 mg/kg, i.p., once, for acute treatment, or 300 μg/10μl/h i.c.v. continuously for 6 days via osmotic minipumps to render rats tolerant to pentobarbital. Rats assigned to the dependent group were sacrificed 24 h after discontinuance of pentobarbital infusion, while those assigned to the tolerant group were sacrificed at the end of infusion. The α6 subunit mRNA was increased in the tolerant group only. Diazepam‐insensitive [3H]Ro15‐4513 binding was increased in the cerebellar granule layer of pentobarbital‐tolerant and ‐dependent rats. No alterations in these parameters were observed in acutely treated animals. These data suggest that chronic pentobarbital treatment induced expression of α6‐subunit mRNA. This was in contrast to α1‐ and γ2‐subunit mRNA, which in tolerant animals are unchanged, but for which withdrawal triggers a surge in levels. Because the α6‐subunit is a major component of the diazepam‐insensitive [3H]Ro15‐4513 binding site, the increased diazepam‐insensitive [3H]Ro15‐4513 binding implied de novo synthesis of the receptor subunit protein. © 1996 Wiley‐Liss, Inc.

show abstract

Thiopentone inhibits beta-adrenergic responses in myocardial tissue

Thurston

Mathew

1995

Can J Anaesth

View full text Add to dashboard Cite

The purpose of this study was to determine the importance of inhibition of beta-adrenergic function in thiopentone-induced myocardial depression. Using an isolated, electrically stimulated rat left atria model, contractile dose-response curves to thiopentone (200 microM, 400 microM, 600 microM, 800 microM) were shifted to the right in preparations treated with 10(-3)M dibutyryl cyclic adenosine monophosphate (cAMP) compared with atria stimulated with 10(-6) M dibutyryl cyclic isoprenaline, demonstrating that inhibition of beta-adrenergic mechanisms by thiopentone is physiologically important. Depression by thiopentone was similar in atria treated with 10(-5) M forskolin compared with preparations stimulated with 10(-6) M isoprenaline, indicating that thiopentone does not block beta-adrenergic receptors. It is concluded that thiopentone depresses myocardial function by several mechanisms, one of which involves inhibition of the adenyl cyclase cascade. The adenyl cyclase enzyme is a likely site where thiopentone inhibits the system; however, other components of the cascade may also be involved.

show abstract

Effective inhibition by pentobarbital of forskolin-stimulated adenylate cyclase activity in rat brain.

Cited by 7 publications

References 0 publications

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

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

Chronic pentobarbital administration alters ?-aminobutyric acidA receptor ?6-subunit mRNA levels and diazepam-insensitive [3H]Ro15-4513 binding

Thiopentone inhibits beta-adrenergic responses in myocardial tissue

Contact Info

Product

Resources

About

Effective inhibition by pentobarbital of forskolin-stimulated adenylate cyclase activity in rat brain.

Cited by 7 publications

References 0 publications

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

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

Chronic pentobarbital administration alters ?-aminobutyric acidA receptor ?6-subunit mRNA levels and diazepam-insensitive [3H]Ro15-4513 binding

Thiopentone inhibits beta-adrenergic responses in myocardial tissue

Contact Info

Product

Resources

About

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

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