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 inh ibitor of the 11 beta-hydroxylase activity or both metyrapone and chlo risondamine. Chlorisondamine induced a significant increase in adrenal weight (31%) without significant rise in hypothalamic CRH content, pl asma 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 si gnificant decrease (90%) of plasma NE and E levels. Chlorisondamine in duced no change in adrenal NPY content as well as NPY mRNA level deter mined by Northern blot but significantly increased NPY plasma level. M etyrapone-treatment induced a significant drop of plasma corticosteron e level and elicited a significant reduction of hypothalamic CRH conte nt, a rise (460%) of the plasma ACTH concentration associated with a s ignificant increase (18%) of the adrenal weight. A marked increase of DA (240%) and significant decrease off (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 treatme nt. Metyrapone elicited a significant increase of adrenal NPY content (88 %) as well as of NPY mRNA revealed by Northern blot analysis but w as unable to significantly affect NPY plasma level. The effects of chl orisondamine, given in combination with metyrapone on both hypothalami c CRH content and plasma ACTH level, were similar to those induced by metyrapone given alone. Chlorisondamine-mediated pharmacological gangl ionic blockade increased metyrapone-induced adrenal hypertrophy and ad renal 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 recepto rs. On the other hand, adrenal TH may be regulated by additional or di fferent mechanisms, which possibly involve nonnicotinic transmission. Present work also suggests that the suppression of the glucocorticoid feedback inhibition of hypothalamic CRH neurons could stimulate sympat honeuronal outflow and consequently elicit transsynaptic cholinergic a ctivation of adrenal neuropeptide Y gene expression.