ACUTE ADMINISTRATION OF HUMAN GALANIN IN NORMAL SUBJECTS REDUCES THE POTENTIATING EFFECT OF PYRIDOSTIGMINE-INDUCED CHOLINERGIC ENHANCEMENT ON RELEASE OF NOREPINEPHRINE AND PANCREATIC-POLYPEPTIDE

The neuropeptide galanin (GAL) is widely distributed in the central an d peripheral nervous systems where it often coexists with catecholamin es and acetylcholine. Recently we have reported that human GAL (hGAL) in man depresses the release of norepinephrine (NE) and the responses to both assumption of upright posture and insulin-induced hypoglycemia . To gain an Acetylcholine insight into the action of hGAL on sympathe tic nervous system activity in man, we investigated the effects of a 6 0-min infusion (80 pmol/kg/min) of hGAL or saline on the release of NE , epinephrine (E) and pancreatic polypeptide (PP) induced by an acetyl cholinesterase inhibitor, pyridostigmine bromide (PD), in nine healthy volunteers. PD (120 mg orally) induced a significant rise in plasma c oncentrations of NE (1.6 +/- 0.04 vs. 1.08 +/- 0.06 nmol/l), E (0.34 /- 0.05 vs. 0.12 +/- 0.04 nmol/l) and PP (178.06 +/- 33 vs. 37.57 +/- 7.35 pmol/l), whilst it significantly reduced heart rate (HR; 61 +/- 2 vs. 71 +/- 4 beats/min). Changes in plasma levels of PP were determin ed as an indirect measure of amplification of endogenous cholinergic a ctivity produced by PD. Administration of hGAL blunted the release of NE and PP evoked by PD. The mean (+/- SEM) area under the curve produc ed by PD of NE (50.05 +/- 3.97 nmol/l . 90 min) and PP (8,692.87 +/- 1 ,724 pmol/l . 90 min) was significantly (p < 0.001) reduced by hGAL in fusion (2.65 +/- 1.57 nmol/l . 90 min and 248.1 +/- 148 pmol/l . 90 mi n, for NE and PP, respectively). hGAL failed to affect significantly t he E release evoked by PD. hGAL was able to enhance HR significantly ( 104 +/- 5 vs. 69 +/- 3 beats/min), and completely prevented the PD-ind uced slowing of HR. Both PD and hGAL did not alter supine systolic and diastolic brood pressure. We conclude that hGAL significantly reduces the release of NE and PP stimulated by PD-induced enhancement of chol inergic activity. These findings are consistent with a functional inte rrelationship between GAL and the cholinergic system in man, and may s uggest the participation of a cholinergic pathway in the galaninergic modulation of the autonomic nervous system.