Volatile anesthetics interfere with muscarinic receptor-g protein interactions in rat heart
The influence of halothane and enflurane (0.5-8%) on muscarinic receptor binding in rat atrium was studied using (/sup 3/H) methylscopolamine ((/sup 3/H)MS). Anesthetic-gas mixtures were blown over membrane suspensions for 20 min before and during the binding assays. Halothane and enflurane increased the affinity of cardiac muscarinic receptors for (/sup 3/H)MS by slowing the rate of dissociation. These anesthetics did not affect the affinity of the receptor for carbamylcholine, but significantly reduced the sensitivity of agonist binding to regulation by guanine nucleotides. For example, the fraction of receptors displaying high affinity agonist binding was decreased by a GTP analog from 0.64 to 0.43 in the absence, but only to 0.52 in the presence of 2% halothane. The binding of a radiolabeled agonist, (/sup 3/H)oxotremorine-M, was reduced by 50% by halothane, while its sensitivity to guanine nucleotides was reduced by at least 100 fold. The diminution of the guanine nucleotide effect may reflect a stabilization of the receptor-G proteincomplex due to either a direct action on the receptor complex or to an alteration of the physical state of the membrane. It is also possible that the ability of the G protein to bind guanine nucleotides is adversely affected by anesthetic agents.
- Research Organization:
- Medical College of Georgia, Augusta (USA)
- OSTI ID:
- 5409564
- Journal Information:
- Ga. J. Sci.; (United States), Vol. 45:2
- Country of Publication:
- United States
- Language:
- English
Similar Records
Muscarinic binding sites in cultured bovine pulmonary arterial endothelial cells
Evidence of paired M2 muscarinic receptors
Related Subjects
ANESTHETICS
BIOLOGICAL EFFECTS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
SYMPATHOMIMETICS
AFFINITY
HEART
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VOLATILITY
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques