Extrahypothalamic corticotropin-releasing hormone mediates (-)-nicotine-induced elevation of plasma corticosterone in rats.
(-)-Nicotine activates the hypothalamic-pituitary-adrenal axis via an activation of the brainstem catecholaminergic neurons in rats. The present study was undertaken to clarify the mechanisms involved in the (-)-nicotine-induced activation of brainstem catecholaminergic neurons in anesthetized rats. Physostigmine (a cholinesterase inhibitor) (0.31 and 0.77 micromol/animal, i.p.) dose-dependently elevated plasma corticosterone in the presence of scopolamine (a muscarinic receptor antagonist) (2.3 micromol/animal, i.p.). (-)-Nicotine (250 and 500 nmol/animal, i.c.v.) dose-dependently elevated plasma corticosterone with concomitant noradrenaline release in the hypothalamic paraventricular nucleus. The (-)-nicotine (500 nmol/animal, i.c.v.)-induced elevation of corticosterone was abolished by phentolamine (an alpha-adrenoceptor antagonist) (0.66 micromol/animal, i.c.v.), and attenuated by (+/-)-sotalol (a beta-adrenoceptor antagonist) (0.97 micromol/animal, i.c.v.). The (-)-nicotine-induced increases of plasma corticosterone and hypothalamic noradrenaline release were abolished either by hexamethonium (a nicotinic acetylcholine receptor antagonist) (1.8 micromol/animal, i.c.v.), CP-154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) (a selective CRF-1 receptor antagonist) (1.3 micromol/animal, i.c.v.) or indomethacin (a cyclooxygenase inhibitor) (1.2 micromol/animal, i.c.v.). These results suggest that (-)-nicotine elevates plasma corticosterone by CRF-1 receptor- and prostaglandin-mediated noradrenaline release in the paraventricular nucleus in rats.
Okada
Shoshiro
S
Department of Pharmacology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Shimizu
Takahiro
T
Yokotani
Kunihiko
K
D000818:Animals; D003345:Corticosterone / Q000097:blood* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D013997:Time Factors; D000099052:CRF Receptor, Type 1
C101628:CP 154526; D016861:Cyclooxygenase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D009538:Nicotine; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone; D009638:Norepinephrine; D007213:Indomethacin