Related Experiment Videos
Acetyl-N-aminodeanol: a cholinergic false transmitter in rat phrenic nerve-diaphragm and guinea-pig myenteric plexus
Abstract:
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.