Agonist regulation of muscarinic acetylcholine receptors in rat spinal cord.
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 [3H]quinuclidinyl benzilate. After a 24-h exposure to carbachol given every 4h, 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.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D010146:Pain; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012684:Sensory Thresholds / Q000187:drug effects; D013116:Spinal Cord / Q000378:metabolism*
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D002217:Carbachol