High-affinity binding of (/sup 3/H)acetylcholine to muscarinic cholinergic receptors

Journal Article · Sat Jun 01 00:00:00 EDT 1985 · J. Neurosci.; (United States)

OSTI ID:5151679

Kellar, K J; Martino, A M; Hall, Jr, D P; Schwartz, R D; Taylor, R L

High-affinity binding of (/sup 3/H)acetylcholine to muscarinic cholinergic sites in rat CNS and peripheral tissues was measured in the presence of cytisin, which occupies nicotinic cholinergic receptors. The muscarinic sites were characterized with regard to binding kinetics, pharmacology, anatomical distribution, and regulation by guanyl nucleotides. These binding sites have characteristics of high-affinity muscarinic cholinergic receptors with a Kd of approximately 30 nM. Most of the muscarinic agonist and antagonist drugs tested have high affinity for the (/sup 3/H)acetylcholine binding site, but pirenzepine, an antagonist which is selective for M-1 receptors, has relatively low affinity. The ratio of high-affinity (/sup 3/H)acetylcholine binding sites to total muscarinic binding sites labeled by (/sup 3/H)quinuclidinyl benzilate varies from 9 to 90% in different tissues, with the highest ratios in the pons, medulla, and heart atrium. In the presence of guanyl nucleotides, (/sup 3/H) acetylcholine binding is decreased, but the extent of decrease varies from 40 to 90% in different tissues, with the largest decreases being found in the pons, medulla, cerebellum, and heart atrium. The results indicate that (/sup 3/H)acetylcholine binds to high-affinity M-1 and M-2 muscarinic receptors, and they suggest that most M-2 sites have high affinity for acetylcholine but that only a small fraction of M-1 sites have such high affinity.

• Research Organization: Georgetown Univ., Washington, DC
• OSTI ID: 5151679
• Journal Information: J. Neurosci.; (United States), Vol. 6
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
CHEMICAL BONDS
AFFINITY
BIOCHEMICAL REACTION KINETICS
CENTRAL NERVOUS SYSTEM
RATS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
DRUGS
ESTERS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
QUATERNARY COMPOUNDS
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques