Acetyl-N-aminodeanol: a cholinergic false transmitter in rat phrenic nerve-diaphragm and guinea-pig myenteric plexus preparations.
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.
Newton
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Ringdahl
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B
Jenden
D J
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D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism; D003964:Diaphragm / Q000294:innervation*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010791:Phrenic Nerve / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism; D013997:Time Factors
D001286:Atropine Derivatives; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; C038146:N-amino-N,N-dimethylaminoethanol; C006649:methylatropine; C038147:O-acetyl-N-amino-N,N-dimethylaminoethanol; D002794:Choline; D000109:Acetylcholine