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Agonist Regulation of Muscarinic Acetylcholine Receptors in Rat Spinal Cord
Author(s) -
Taylor John E.,
Yaksh Tony L.,
Richelson Elliott
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb03975.x
Subject(s) - muscarinic acetylcholine receptor , carbachol , muscarinic acetylcholine receptor m4 , endocrinology , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m3 , medicine , chemistry , quinuclidinyl benzilate , agonist , atropine , muscarinic acetylcholine receptor m1 , muscarinic antagonist , muscarinic acetylcholine receptor m5 , receptor , pharmacology , biology
In vitro studies with cultured cells originating from nervous tissue have shown that chronic exposure to muscarinic agonists results in a loss of muscarinic receptors. To determine whether this type of regulation of muscarinic receptor number also occurs in vivo , we infused carbachol into the spinal cords of rats. A single carbachol injection into the lumbar spinal cord caused a significant increase in the nociceptive threshold. This effect of carbachol diminished to control levels after 12 h of repeated agonist injections every 4 h and was blocked by atropine. The desensitization to the antinociceptive effects of carbachol was associated with a loss of muscarinic receptors as determined by the binding of the muscarinic antagonist [ 3 H]quinuclidinyl benzilate. After a 24‐h exposure to carbachol given every 4 h, there was about a 60% loss of binding sites. The loss of muscarinic receptors was also blocked by atropine and was reversible. These results represent direct evidence that a muscarinic agonist can regulate receptor number in the central nervous system and suggest that this loss of receptors is associated with a desensitization to the antinociceptive effects of carbachol injected into the spinal cord.