Effect of cholinergic blockade on glucocorticoid regulation of NPY and catecholamines in the rat adrenal gland.
Catecholamines and neuropeptide Y (NPY) levels were determined in the adrenals of rats treated for 2.5 days with chlorisondamine (6 mg/day), a nicotinic ganglionic blocking agent, metyrapone (66 mg/day), an inhibitor of the 11 beta-hydroxylase activity or both metyrapone and chlorisondamine. Chlorisondamine induced a significant increase in adrenal weight (31%) without significant rise in hypothalamic CRH content, plasma ACTH level and plasma corticosterone concentration. This drug was unable to affect significantly dopamine (DA), norepinephrine (NE) and epinephrine (E) content of the adrenals; in contrast, it induced a significant decrease (90%) of plasma NE and E levels. Chlorisondamine induced no change in adrenal NPY content as well as NPY mRNA level determined by Northern blot but significantly increased NPY plasma level. Metyrapone-treatment induced a significant drop of plasma corticosterone level and elicited a significant reduction of hypothalamic CRH content, a rise (460%) of the plasma ACTH concentration associated with a significant increase (18%) of the adrenal weight. A marked increase of DA (240%) and significant decrease of E (22%) in the adrenal gland were observed in response to metyrapone treatment. In addition, metyrapone induced a drop (23%) in plasma E level. In both the adrenals and the plasma, the ratio E/NE was significantly reduced by metyrapone treatment. Metyrapone elicited a significant increase of adrenal NPY content (88%) as well as of NPY mRNA revealed by Northern blot analysis but was unable to significantly affect NPY plasma level. The effects of chlorisondamine, given in combination with metyrapone on both hypothalamic CRH content and plasma ACTH level, were similar to those induced by metyrapone given alone. Chlorisondamine-mediated pharmacological ganglionic blockade increased metyrapone-induced adrenal hypertrophy and adrenal DA storage but prevented metyrapone-induced depletion of adrenal E as well as increase of the adrenal NPY mRNA level and NPY content. Chlorisondamine-induced elevation of plasma NPY level was not observed under metyrapone treatment. Present data suggest that the increase in adrenal NPY synthesis in response to metyrapone treatment is mediated by transsynaptic cholinergic activation and implies nicotinic receptors. On the other hand, adrenal TH may be regulated by additional or different mechanisms, which possibly involve nonnicotinic transmission. Present work also suggests that the suppression of the glucocorticoid feedback inhibition of hypothalamic CRH neurons could stimulate sympathoneuronal outflow and consequently elicit transsynaptic cholinergic activation of adrenal neuropeptide Y gene expression.
Laborie
C
C
Centre de Biologie Cellulaire, Neuroendocrinologie du Développement, SN4, Université de Lille 1, Villeneuve d'Ascq, France.
Bernet
F
F
Dutriez-Casteloot
I
I
Lesage
J
J
Dupouy
J P
JP
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002395:Catecholamines / Q000378:metabolism*; D002714:Chlorisondamine / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004347:Drug Interactions; D005730:Ganglionic Blockers / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009478:Neuropeptide Y / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002395:Catecholamines; D018680:Cholinergic Antagonists; D005730:Ganglionic Blockers; D005938:Glucocorticoids; D009478:Neuropeptide Y; D002714:Chlorisondamine; D008797:Metyrapone