Nicotinic agonists administered into the fourth ventricle stimulate norepinephrine secretion in the hypothalamic paraventricular nucleus: an in vivo microdialysis study.
Nicotinic cholinergic agonists stimulate ACTH secretion by a central mechanism involving brainstem catecholamines. In vivo microdialysis studies were conducted to measure the release of norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) in response to the administration of nicotine (Nic) or another nicotinic cholinergic (NAch) agonist, cytisine (Cyt), directly into the IVth ventricle. Alert, freely mobile rats, equipped 24 h previously with a chronic guide cannula in the IVth ventricle and microdialysis probe in the PVN, were injected with artificial cerebrospinal fluid (CSF, 500 nl/60 s), Nic (1-5 micrograms), or Cyt (1-25 micrograms) after three 20-min baseline samples had been taken. Analysis of the dialysates by HPLC with electrochemical detection demonstrated the dose-dependent secretion of PVN NE to Nic or Cyt with ED50s of approximately 1 or 6 micrograms, respectively; these were completely blocked by prior IVth ventricular injection of the NAch antagonist, mecamylamine (4 micrograms). In contrast, alpha-bungarotoxin, which antagonizes the action of NAch agonists by acting through the alpha 7 bungarotoxin-type NAchR, failed to reduce the NE response to Nic. Partial, but significant desensitization of NE secretion in response to a second injection of Nic (2.5 or 5 micrograms) 100 min after the first was seen, whereas NE responses to the second injection of Cyt (5 or 25 micrograms) were completely desensitized. However, cross-desensitization of each agonist to the other did not occur. This may reflect heterogeneity of the NAch receptor subtypes involved. The results of this study establish a correlation between the action of nicotine on brainstem norepinephrinergic regions and the resultant release of NE in the PVN, which would lead to the release of ACTH secretagogues.
Matta
S G
SG
Endocrine-Neuroscience Laboratories, Minneapolis Medical Research Foundation, MN 55404, USA.
McCoy
J G
JG
Foster
C A
CA
Sharp
B M
BM
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D001933:Brain Stem / Q000502:physiology*; D002038:Bungarotoxins / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000819:agonists* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D011807:Quinolizines; D051381:Rats; D011919:Rats, Inbred Strains; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D002038:Bungarotoxins; D009538:Nicotine; D009638:Norepinephrine; D011807:Quinolizines; C004712:cytisine; D000093843:Quinolizidine Alkaloids