Acetylcholine receptors do not mediate isoflurane's actions on spinal cord in vitro.
Extensive studies on anesthetic mechanisms have focused on the nicotinic acetylcholine receptor, and to a lesser extent on the muscarinic receptor. We designed the present study to test the hypothesis that cholinergic receptors mediate some of the depressant actions of a volatile anesthetic in rat spinal cord. The cord was removed from 2- to 7-day-old rats and superfused in vitro; ventral root potentials were evoked by stimulating a lumbar dorsal root and recording from the corresponding ipsilateral ventral root. Both nicotine and muscarine depressed the nociceptive-related slow ventral root potential (sVRP). The nicotinic antagonists mecamylamine, methyllycaconitine, dihydro-beta-erythroidine, and the muscarinic antagonist atropine blocked the depressant effects of the respective agonists. Isoflurane 0.3 mini- mum alveolar anesthetic concentration depressed the sVRP area to approximately 40% of control. None of the antagonists changed the extent of isoflurane depression of the sVRP. The depressant actions of cholinergic agonists suggest that cholinergic receptors are important in spinal neurotransmission, but the lack of interaction between antagonists and isoflurane suggests that cholinergic receptors have little part in mediating the actions of this anesthetic in spinal cord. Because minimum alveolar anesthetic concentration is determined primarily in spinal cord, cholinergic receptors may be eliminated as molecular targets for this anesthetic end-point.


CONCLUSIONS
Neither nicotinic nor muscarinic acetylcholine receptor antagonists altered spinal cord actions of isoflurane, suggesting that these receptors have little role in isoflurane actions in spinal cord. Cholinergic receptors thus may be eliminated as molecular targets in determining the anesthetic end-point of immobility in response to a noxious stimulus (minimum alveolar anesthetic concentration).
Wong
Shirley M E
SM
Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305-5117, USA.
Sonner
James M
JM
Kendig
Joan J
JJ
D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007530:Isoflurane / Q000378:metabolism / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D007530:Isoflurane