DIFFERENTIAL IN-VIVO REGULATION OF MESSENGER-RNA ENCODING THE NOREPINEPHRINE TRANSPORTER AND TYROSINE-HYDROXYLASE IN RAT ADRENAL-MEDULLA AND LOCUS-CERULEUS

To investigate the regulation of norepinephrine transporter mRNA in vi vo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and locus ceruleus. First, PCR was used to clone a 0.5 -kb rat cDNA fragment that exhibits 87% nucleotide identity to the cor responding human norepinephrine transporter cDNA sequence. In situ, th e cDNA hybridizes specifically with in norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepin ephrine transporter mRNA in the adrenal medulla by similar to 65% and in the locus ceruleus by similar to 25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not det ect the smaller changes observed in the locus ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and locus ceruleus. These results suggest that noradr energic neurons and adrenal chromaffin cells can coordinate opposing c hanges in systems mediating catecholamine uptake and synthesis, to com pensate for catecholamine depletion.