HIGH-AFFINITY BINDING OF ACETYLCHOLINE-H-3 TO MUSCARINIC RECEPTORS - REGIONAL DISTRIBUTION AND MODULATION BY GUANINE-NUCLEOTIDES

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 28  (3) , 297-305
Abstract
The interaction of [3H]acetylcholine ([3H]AcCh) with the muscarinic receptor was studied in seven distinct rat brain regions and in heart atrium by employing 10 .mu.M atropine to define specific binding. The specific binding exhibited by the labeled neurotransmitter was found to be sensitive to muscarinic but not to nicotinic drugs. The muscarinic high affinity agonist-binding sites were characterized with respect to their binding properties, regional distribution, pharmacology, and modulation by guanyl nucleotides and by transition metal ions. In all tissues examined, specific binding of [3H]AcCh was saturable over the range of 4-200 nM and occurred in a receptor population that was apparently homogeneous and had a dissociation constant of approximately 19-39 nM in most of the regions. The ratio of muscarinic receptors labeled by [3H]AcCh to those labeled by the potent antagonist [3H]N-methyl-4-piperidylbenzilate varied markedly among tissues, from 0.15 in the hippocampus to 0.71 in the atrium. This ratio was lower in brain regions rich in muscarinic receptors, where smaller sensitivity of [3H]AcCh binding to guanyl nucleotides was also observed. In the presence of the latter [3H]AcCh binding was decreased by 25 to 90% in different tissues, with the greatest decreases occurring in the atrium and brainstem. In the latter preparations, transition metal ions do not affect [3H]AcCh binding, while in the other preparations studied they induce an increase in the binding capacity for the labeled neurotransmitter, which is sensitive to guanine nucleotides.