Role of brain nicotinic acetylcholine receptor in centrally administered corticotropin-releasing factor-induced elevation of plasma corticosterone in rats.
The present study was undertaken to clarify the central mechanisms involved in the intracerebroventricularly administered corticotropin-releasing factor-induced elevation of plasma corticosterone in urethane- and alpha-chloralose-anesthetized rats using microdialysis and immunohistochemical techniques. When corticotropin-releasing factor was given at 0.5, 1.5, and 3.0 nmol/animal intracerebroventricularly, it dose-dependently increased noradrenaline release but not adrenaline release in the hypothalamic paraventricular nucleus. The 1.5 nmol/animal dose of corticotropin-releasing factor-induced noradrenaline release was attenuated by CP-154,526 (butyl-ethyl-{2,5-dimethyl-7-(2,4,6 trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amine), a selective corticotropin-releasing factor receptor 1 antagonist, at 1.3 micromol/animal, intracerebroventricularly, and was also abolished by phentolamine at 0.66 micromol/animal, intracerebroventricularly. In addition, the corticotropin-releasing factor-induced elevation of noradrenaline release in the hypothalamic paraventricular nucleus and plasma corticosterone were abolished by hexamethonium, a non-selective nicotinic acetylcholine receptor antagonist, at 1.8 micromol/animal, intracerebroventricularly, and alpha-conotoxin MII, a potent alpha(3)beta(2) nicotinic acetylcholine receptor antagonist, at 30 nmol/animal, i.c.v. Corticotropin-releasing factor at 1.5 nmol/animal, i.c.v. evoked a significant expression of Fos, an immediate-early transcription factor in neurons, on the dopamine-beta-hydroxylase-containing neurons and alpha(3) nicotinic acetylcholine receptor subunit-expressing neurons in the locus coeruleus, but not in the medullary A(1) and A(2) regions containing noradrenergic neurons. These results suggest that centrally administered corticotrophin-releasing factor elevates plasma corticosterone by the corticotropin-releasing factor 1 receptor and alpha(3) subunit-containing nicotinic acetylcholine receptor (probably alpha(3)beta(2) nicotinic acetylcholine receptor) mediated activation of the locus coeruleus noradrenergic neurons projecting to the paraventricular nucleus in rats.
Okada
Shoshiro
S
Department of Pharmacology, Graduate School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan. okadas@kochi-u.ac.jp
Yamaguchi-Shima
Naoko
N
Shimizu
Takahiro
T
Arai
Junichi
J
Lianyi
Lu
L
Wakiguchi
Hiroshi
H
Yokotani
Kunihiko
K
D000302:Adrenal Cortex / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D020916:Conotoxins / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005730:Ganglionic Blockers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D020916:Conotoxins; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D011978:Receptors, Nicotinic; C098872:alpha-conotoxin MII; D003346:Corticotropin-Releasing Hormone; D004299:Dopamine beta-Hydroxylase; D003345:Corticosterone; D010646:Phentolamine