Investigation on regulatory mechanism of acetylcholine release at cholinergic nerve endings.

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To investigate subtypes of nuscarinic receptor regulating acetylcholine (ACh) release at cholinertic nerve endings, a radioimmunoassay (RIA) for ACh was applied to the direct determination of ACh release in longitudinal muscle strips of guinea pig ileum. The strips were preincubated with irreversible cholinesterase inhibitor and superfused with Kreds' solution under various experimental conditions. Pirenzepine (PZ), a specific M_1 antagonist, produced an increase in electrically evoked ACh release at a concentrtion of 100-times less than that inhibiting the electrically evoked contractile response. On the other hand, atropine (AT), a nonspecific muscarinic antagonist, produced an inhibition of presynaptic muscarinic receptors at a concentration of 10-fold less than that inhibiting postsynaptic muscarinic receptors. These results suggest that presyn aptic M_1 receptors regulating ACh release may be present in the guinea pig ileum.To confirm our previous data, the effect of three muscari … More nic antagonists on electrically evoked ACh release and contractile response were investigated in the same preparation. Telenzapine (TZ), a selective M_1 antagonist, increased electrically evoked ACh release at a concentration of 100-fold less than that inhiditing the contractile response. AF-DX 116, a cardioselective M_2 entagonist, inhibited the contractile response at 10 uM, but did not affect electrically evoked ACh release at this concentration. (-)N-Methylscopolamine (NMS) produced an inhibition of the contractile response without any effect on ACh release. The data-obtained in the present and previous studies demonstrate that presynaptic muscarinic receptors modulating ACh release can be classified as M_1 subtype.To examine effect of TRH on ACh release in the central nervous system, high potassium (50 mM)-evoked ACh release from rat basal forebrain slices was betermined using a RIA. TRH (100 uM) caused a slight and statistically insignificant increase in potassium-evoked ACh release. DN-1417, a TRH analogue, at a concentration of 100 uM increased potassium-evoked ACh release significantly. These findings indicate that DN-1417 is able to increase ACh release in the central nervous system at a high concentration. Less