DEXAMETHASONE DOWN-REGULATES THE EXPRESSION OF ENDOTHELIN-B RECEPTOR MESSENGER-RNA IN THE RAT-BRAIN

The present study was designed to examine effects of dexamethasone on the steady state level of endothelin B(ETB) receptor mRNA in in vivo the rat brain. ETB receptor mRNA was very high at the hypothalamus and cerebellum but was comparatively low at the striatum and amygdala. Dexamethasone, 1 and 7 mg/kg, i.p., markedly and dose-relatedly decreased ETB receptor mRNA level with slow onset of 8hr at the hypothalamus and cerebellum, but did not induced a marked decrease at other areas. On the contrary, dexamethasone produced an increase of ET-1 mRNA which preceded to the decrease of ETB receptor mRNA at the same brain areas. Phosphoramidon, a endothelin-converting enzyme inhibitor, did not antagonized but potentiated the effect of dexamethasone. Besides, phosphoramidon per se markedly stimulated the expression of ET-1 mRNA. The results suggested that dexamethasone down-regulates ETB receptor mRNA level at the hypothalamus and cerebellum of rat brain and these effects may be involved in the increase of ET-1 peptide gene transcription.