degli Uberti E C, Bondanelli M, Margutti A, Ambrosio M R, Valentini A, Campo M, Franceschetti P, Zatelli M C, Pansini R, Trasforini G
Chair of Endocrinology, University of Ferrara, Italy.
Neuroendocrinology. 1996 Nov;64(5):398-404. doi: 10.1159/000127143.
The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems where it often coexists with catecholamines 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 insight into the action of hGAL on sympathetic nervous system activity in man, we investigated the effects of a 60-min infusion (80 pmol/kg/min) of hGAL or saline on the release of NE, epinephrine (E) and pancreatic polypeptide (PP) induced by an acetylcholinesterase inhibitor, pyridostigmine bromide (PD), in nine healthy volunteers. PD (120 mg orally) induced a significant rise in plasma concentrations 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 determined as an indirect measure of amplification of endogenous cholinergic activity produced by PD. Administration of hGAL blunted the release of NE and PP evoked by PD. The mean (+/- SEM) area under the curve produced 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 infusion (2.65 +/- 1.57 nmol/l.90 min and 248.1 +/- 148 pmol/l.90 min, for NE and PP, respectively). hGAL failed to affect significantly the E release evoked by PD. hGAL was able to enhance HR significantly (104 +/- 5 vs. 69 +/- 3 beats/min), and completely prevented the PD-induced slowing of HR. Both PD and hGAL did not alter supine systolic and diastolic blood pressure. We conclude that hGAL significantly reduces the release of NE and PP stimulated by PD-induced enhancement of cholinergic activity. These findings are consistent with a functional interrelationship between GAL and the cholinergic system in man, and may suggest the participation of a cholinergic pathway in the galaninergic modulation of the autonomic nervous system.
神经肽甘丙肽（GAL）广泛分布于中枢和外周神经系统，常与儿茶酚胺和乙酰胆碱共存。最近我们报道，人体内的人甘丙肽（hGAL）可抑制去甲肾上腺素（NE）的释放以及对直立姿势和胰岛素诱导的低血糖的反应。为深入了解hGAL对人体交感神经系统活动的作用，我们在9名健康志愿者中研究了静脉输注60分钟hGAL（80 pmol/kg/min）或生理盐水对溴化吡啶斯的明（PD）诱导的NE、肾上腺素（E）和胰多肽（PP）释放的影响。口服PD（120 mg）可使血浆NE浓度显著升高（1.6±0.04 vs. 1.08±0.06 nmol/l）、E浓度显著升高（0.34±0.05 vs. 0.12±0.04 nmol/l）以及PP浓度显著升高（178.06±33 vs. 37.57±7.35 pmol/l），同时显著降低心率（HR；61±2 vs. 71±4次/分钟）。测定PP血浆水平的变化作为PD诱导的内源性胆碱能活性增强的间接指标。输注hGAL可减弱PD引起的NE和PP释放。hGAL输注使PD诱导的NE曲线下平均（±SEM）面积（50.05±3.97 nmol/l·90分钟）和PP曲线下平均（±SEM）面积（8,692.87±1,724 pmol/l·90分钟）显著（p<0.001）降低（NE和PP分别为2.65±1.57 nmol/l·90分钟和248.1±148 pmol/l·90分钟）。hGAL对PD诱导的E释放无显著影响。hGAL能够显著提高心率（104±5 vs. 69±3次/分钟），并完全防止PD引起的心率减慢。PD和hGAL均未改变仰卧位收缩压和舒张压。我们得出结论，hGAL显著降低了PD诱导的胆碱能活性增强所刺激的NE和PP释放。这些发现与人中GAL和胆碱能系统之间的功能相互关系一致，并可能提示胆碱能途径参与了甘丙肽能对自主神经系统 的调节。
