RU486 blocks fasting-induced decrease of neuronal nitric oxide synthase in the rat paraventricular nucleus.
It has been reported that food deprivation decreases expression of neuronal nitric oxide synthase (nNOS) in the hypothalamic paraventricular nucleus (PVN). Food deprivation produces autonomic changes and the PVN nitric oxide has been suggested to be involved in regulation of autonomic functions. In order to understand the molecular mechanism by which food deprivation decreases nNOS expression in the PVN, we examined if plasma glucocorticoids, which reported to be elevated during food deprivation, mediates the fasting-induced down-regulation of the PVN-nNOS. Male Sprague-Dawley rats underwent 48 h of food deprivation, but not water deprivation, with/without subcutaneous RU486, glucocorticoid receptor antagonist, and the brain tissues were processed for immunohistochemistry with specific antibodies against nNOS. Immunoreactivity of phosphorylated cAMP response element-binding protein (pCREB) was also examined in the PVN sections, because nNOS promoter carries cAMP response element (CRE). Food deprivation significantly decreased both nNOS and pCREB immunoreactivity (-ir) in the medial parvocellular PVN, and RU486 blocked this reduction. In the posterior magnocellular PVN, nNOS-ir, but not pCREB-ir, was decreased by food deprivation, and RU486 exerted no effect. These results suggest that glucocorticoid receptor may mediate the fasting-induced down-regulation of nNOS in the parvocellular PVN, but not in the magnocellular PVN.
Department of Pharmacology and BK 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Yun Mi
YM
Kim
Joo Young
JY
Lee
Si Ho
SH
Choi
Dong Goo
DG
Kim
Jeong Won
JW
Jahng
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation; D005215:Fasting / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
D017362:Cyclic AMP Response Element-Binding Protein; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat