Rapid decrease in neuropeptide Y gene expression in rat adrenal gland induced by the alpha 2-adrenoceptor agonist, clonidine.

1 The mechanism of regulation of the neuropeptide Y (NPY) gene by pharmacological treatment with the alpha 2-adrenenoceptor agonist, clonidine, was investigated by quantitative Northern blot analysis of the effects of this drug on the NPY mRNA levels in rat adrenal gland and medulla oblongata/pons. 2 In the adrenal gland, clonidine-treatment (50 microgram kg-1, s.c., once daily) resulted in decrease in the amount of NPY mRNA to 44 +/- 10% of the control level in 24 h and then its increase to 162 +/- 16% of the control level after 5 days. Concomitant changes in putative NPY pre-mRNA species (7.0 and 3.3 kb) were observed, probably due to changes at the level of NPY gene transcription. 3 The short-term (24 h) effect of clonidine was blocked by yohimbine (5 mg kg-1, i.p., once daily). Yohimbine alone tended to increase the NPY mRNA level after 24h. 4 The recovery/increase in the NPY mRNA level in the adrenal gland after 5 days treatment with clonidine was similar to its increase after treatment with reserpine (0.5 mg kg-1, i.p., once daily). 5 NPY gene expression in the medulla oblongata/pons was not changed by short- or long-term treatment with clonidine. 6 These results suggest that clonidine suppresses NPY gene expression in the adrenal gland, probably at the level of transcription, by activation of the alpha 2-adrenoceptor.