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Acetyl-N-aminodeanol: a cholinergic false transmitter in rat phrenic nerve-diaphragm and guinea-pig myenteric plexus preparations

MW Newton, B Ringdahl and DJ Jenden

The metabolism of the choline analog N-amino-N,N-dimethylaminoethanol (N-aminodeanol) by isolated rat diaphragm and guinea-pig myenteric plexus preparations and the pharmacological properties of the acetate ester were studied. Deuterium-labeled N-aminodeanol was transported and acetylated by rat diaphragm and guinea-pig myenteric plexus preparations. Diaphragms stimulated indirectly in the presence of [2H4]N-aminodeanol (2 X 10(-5) M) released [2H4]acetyl-N-aminodeanol at 38% the rate at which [2H4]acetylcholine was released from controls incubated with [2H4]choline (2 X 10(-5) M). In the guinea-pig myenteric plexus, [2H4]acetyl-N-aminodeanol was synthesized and released at a rate up to 70% that measured for [2H4] acetylcholine. N-methylatropine (10(-7) M) enhanced the stimulated release of [2H4]acetyl-N-aminodeanol and [2H4] acetylcholine (in separate controls) by the same amount (2,3- fold). After incubation in the presence of [2H4]N-aminodeanol, [2H4]acetyl-N-aminodeanol replaced (mole for mole) 17 and 50% of the endogenous acetylcholine tissue content in diaphragm and myenteric plexus, respectively. As the tissue [2H0]acetylcholine was replaced, its release was reduced to 38 and 22% of control in diaphragm and myenteric plexus, respectively. Combined transmitter release (true + false) was reduced to 56 to 79% of release from controls. Endogenous choline efflux apparently limited the replacement of true with false transmitter in these preparations. Acetyl-N-aminodeanol had 4 and 17% the potency of acetylcholine on the guinea-pig ileum and frog rectus abdominis preparations, respectively. These findings indicate that [2H4]N-aminodeanol forms a false transmitter in rat diaphragm and guinea-pig myenteric plexus and may potentially interfere with cholinergic function. Effective replacement of endogenous acetylcholine in vivo would also require replacement of endogenous sources of choline for transmitter synthesis.

Volume 235, Issue 1, pp. 147-156, 10/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1985 by the American Society for Pharmacology and Experimental Therapeutics.