Cholinergic potentiation of the meal-related rise in ACTH and Cortisol concentrations in men

 

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Summary

The present study examined the influence of physostigmine, an acetylcholine esterase inhibitor, on the secretory activity of the hypothalamo-pituitary-adreno-cortical (HPA) — axis under basal (experiment I) and stimulated (experiment II) conditions in young healthy men. In a third experiment, the effect of scopolamine, a muscarinic acetylcholine receptor antagonist, on HPA secretory activity after physiological stimulation was tested.

The experiments started between 09.00 and 10.00 a.m. After a resting period of 1.5 h, either physostigmine (0.0125 mg per kg body weight soluted in isotonic saline) or placebo (saline) was infused within 15 min. In experiment I subjects (n=7) remained fasting while in experiment II (n=18) a standardized lunch was offered after the infusion. Experiment III (n=7) was designed as experiment II but instead of physostigmine, scopolamine or placebo (0.5 mg) was subcutaneously injected 105 min before the meal. Blood for the determination of ACTH and Cortisol was drawn in regular intervals during the experiments.

Physostigmine did not change basal ACTH and Cortisol secretion per se, excluding activation of basal HPA secretion due to acetylcholineesterase inhibition and its non specific side effects. Meal intake stimulated ACTH and Cortisol secretion which was significantly enhanced when physostigmine was administered (p<0.05). Scopolamine did not influence the meal related ACTH and Cortisol secretion.

These findings demonstrate that cholinergic neurotransmission is able to increase ACTH and Cortisol concentrations in humans. This effect seems to be complementary to other stimulatory neurotransmitter systems, and is functional during stimulated HPA secretory activity and not under basal conditions.