Nonopioid effect of morphine on electrically evoked acetylcholine release from Torpedo electromotor neurons.
The release of acetylcholine from Torpedo electric organ slices following their electrical stimulation was modulated by morphine, by the muscarinic antagonist atropine, and by the nicotinic antagonist tubocurarine. Addition of either atropine or tubocurarine in the presence of the acetylcholinesterase inhibitor phospholine iodide enhanced acetylcholine release. The effects of the two antagonists were additive, a result suggesting that the secreted acetylcholine regulates its own release by activating both muscarinic and nicotinic cholinergic receptors and that these receptors inhibit acetylcholine release by different mechanisms. The effects of opiates on acetylcholine release were examined under conditions in which the cholinergic modulation of release is blocked, i.e., in the presence of atropine and tubocurarine. These experiments revealed that electrically evoked release of acetylcholine is blocked by the opiate agonists morphine and levorphanol. However, the inhibitory effect of morphine on acetylcholine release was not reversed by the opioid antagonist naloxone. Furthermore, dextrorphan, the nonopioid stereoisomer of levorphanol, had the same inhibitory effect as its opioid counterpart. These findings suggest that the effects of opiates on electrically evoked release of acetylcholine are not mediated by opioid receptors. The possible mechanisms underlying these nonopioid effects of morphine and levorphanol are discussed.
Oron
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Department of Biochemistry, George S. Wise Faculty of Life Sciences, Ramat Aviv, Israel.
Sarne
Y
Y
Michaelson
D M
DM
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004456:Echothiophate Iodide / Q000494:pharmacology; D004557:Electric Organ / Q000294:innervation*; D004558:Electric Stimulation / Q000379:methods; D007981:Levorphanol / Q000494:pharmacology; D008024:Ligands; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D013237:Stereoisomerism; D014101:Torpedo / Q000378:metabolism*; D014403:Tubocurarine / Q000494:pharmacology
D008024:Ligands; D009294:Narcotics; D007981:Levorphanol; D009020:Morphine; D001285:Atropine; D004456:Echothiophate Iodide; D000109:Acetylcholine; D014403:Tubocurarine