Piperidine enhances sleep-related and insulin-induced growth hormone secretion: further evidence for a cholinergic secretory mechanism.

Piperidine, a nicotinic cholinergic receptor stimulator, was used in paired design studies of sleep-related and insulin-induced GH and PRL secretion. For the sleep studies, 100 mg piperidine or an equal volume of saline were infused for 30 min starting at sleep onset in eight normal volunteers. The same dose of piperidine was infused for 30 min (beginning 15 min before insulin injection) in an additional eight volunteers undergoing insulin tolerance tests. After piperidine administration, there was a significant (P less than 0.01) enhancement of sleep-related GH secretion, abut no change in PRL. GH concentrations during the first 2 h of sleep were 7.2 +/- 1.2 ng/ml after saline and 15.2 +/-2.9 ng/ml after piperidine (P less than 0.01). No alteration in any measured sleep parameter was noted with the drug. Piperidine did not affect the daytime insulin-induced secretion of either GH or PRL, as assessed by an analysis of variance. However, paired analysis of increments and areas under the response curves indicated a statistically significant effect for GH but not PRL. The maximum GH increment with piperidine was 48.0 +/- 4.3 ng/ml, compared to 36.8 +/- 3.6 ng/ml with saline (P less than 0.01). Piperidine given alone did not influence daytime concentrations of GH. These data are consistent with the view proposed by us, on the bass of methoscopolamine inhibition of nocturnal GH secretion, that cholinergic pathways play a facilitatory role in sleep-related and insulin-induced GH secretion. Thus, cholinergic mechanisms stimulate GH secretion. Nicotinic as well as muscarinic pathways appear to be involved, although the quantitative nicotinic contribution seems to be smaller than the associated with muscarinic sites.