α₁-Adrenergic receptor-mediated downregulation of angiotensin II receptors in neuronal cultures

Previous evidence has suggested that brain catecholamine levels are important in the regulation of central angiotensin II receptors. In the present study, the effects of norepinephrine and 3,4-dihydroxyphenylethylamine (dopamine) on angiotensin II receptor regulation in neuronal cultures from rat hypothalamus and brainstem have been examined. Both catecholamines elicit significant decreases in [125I]angiotensin II-specific binding to neuronal cultures prepared from normotensive rats, effects that are dose dependent and that are maximal within 4-8 h of preincubation. Saturation and Scatchard analyses revealed that the norepinephrine-induced decrease in the binding is due to a decrease in the number of angiotensin II receptors in neuronal culturs, with little effect on the receptor affinity. Norepinephrine has no significant actions on [125I]angiotensin II binding in cultures prepared from spontaneously hypertensive rats. The downregulation of angiotensin II receptors by norepinephrine or dopamine is blocked by α1-adrenergic and not by other adrenergic antagonists, a result suggesting that this effect is initiated at the cell surface involving α1-adrenergic receptors. This is further supported by our data indicating a parallel downregulation of specific α1-adrenergic receptors elicited by norepinephrine. In summary, these results show that norepinephrine and dopamine are able to alter the regulation of neuronal angiotensin II receptors by acting at α1-adrenergic receptors, which is a novel finding.

Duke Scholars

Author Lana L. Watkins Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...