Open AccessBatrachotoxin changes the properties of the muscarinic receptor in rat brain and heart: possible interaction(s) between muscarinic receptors and sodium channels.
Author(s) -
Malka Cohen-Armon,
Yoel Kloog,
Yoav I. Henis,
Mordechai Sokolovsky
Publication year - 1985
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.82.10.3524
Subject(s) - muscarinic acetylcholine receptor , oxotremorine , chemistry , agonist , batrachotoxin , binding site , muscarinic acetylcholine receptor m1 , acetylcholine , muscarinic acetylcholine receptor m4 , dibucaine , muscarinic acetylcholine receptor m2 , acetylcholine receptor , receptor , biophysics , endocrinology , medicine , biochemistry , sodium channel , sodium , biology , organic chemistry
The effects of Na+-channel activator batrachotoxin (BTX) on the binding properties of muscarinic receptors in homogenates of rat brain and heart were studied. BTX enhanced the affinity for the binding of the agonists carbamoylcholine and acetylcholine to the muscarinic receptors in brainstem and ventricle, but not in the cerebral cortex. Analysis of the data according to a two-site model for agonist binding indicated that the effect of BTX was to increase the affinity of the agonists to the high-affinity site. Guanyl nucleotides, known to induce interconversion of high-affinity agonist binding sites to the low-affinity state, canceled the effect of BTX on carbamoylcholine and acetylcholine binding. BTX had no effect on the binding of the agonist oxotremorine or on the binding of the antagonist [3H]-N-methyl-4-piperidyl benzilate. The local anesthetics dibucaine and tetracaine antagonized the effect of BTX on the binding of muscarinic agonists at concentrations known to inhibit the activation of Na+ channels by BTX. On the basis of these findings, we propose that in specific tissues the muscarinic receptors may interact with the BTX binding site (Na+ channels).