Norepinephrine metabolism in neuronal cultures is increased by angiotensin II

In this study we have examined the actions of angiotensin II (ANG II) on catecholamine metabolism in neuronal brain cell cultures prepared from the hypothalamus and brain stem. Neuronal cultures prepared from the brains of 1-day-old Sprague-Dawley rats exhibit specific neuronal uptake mechanisms for both norepinephrine (NE) and dopamine (DA), and also monoamine oxidase (MAO) and catechol O-methyltransferase (COMT) activity. Separate neuronal uptake sites for NE and DA were identified by using specific neuronal uptake inhibitors for each amine. In previous studies, we determined that ANG II (10 nM-1 microM) stimulates increased neuronal [3H]NE uptake by acting at specific receptors. We have confirmed these results here and in addition have shown that ANG II (1 nM-10 microM, 10-120 min) has no significant effects on neuronal [3H]DA uptake. These results suggest that the actions of ANG II are restricted to the NE transporter in neuronal cultures. It is possible that ANG II stimulates the intraneuronal metabolism of at least part of the NE that is taken up, because the peptide stimulates MAO activity, an effect mediated by specific ANG II receptors. ANG II had no effect on COMT activity in neuronal cultures. Therefore, the use of neuronal cultures of hypothalamus and brain stem we have determined that ANG II can specifically alter NE metabolism in these areas, while apparently not altering DA metabolism.