Reversal of noradrenaline denervation-induced increase of beta-adrenoreceptor binding in rat neocortex by noradrenaline infusion

The effect of intraventricular infusion of (-)-noradrenaline (NA) on beta-receptor binding in vitro to homogenates from 6-hydroxydopamine (6-OH-DA)-denervated and from normal rat cerebral cortex was studied. NA was infused with osmotic minipumps connected to cannulas placed in the right lateral ventricle, delivering 1 or 5 microgram (-)-NA/h continuously for 9 days. One day later the rats were sacrificed and cortical tissue taken for beta-receptor (using 3H]dihydroalprenolol (3H]DHA) as radioligand) and NA assay. The NA level in the cerebral cortex of 6-OH-DA treated rats was decreased to 70-80% of that of controls. No substantial change in the NA level was observed after infusion of 1 microgram (-)-NA/h, whereas infusion of 5 microgram/h led to a 40-60% increase compared to that of control rats infused with vehicle alone. Infusion of vehicle alone into control rats did not cause any change in 3H]DHA binding, whereas in denervated rats there was a 30-50% increase in 3H]DHA binding compared to that of controls. This increase was completely counteracted by infusion of 1 or 5 microgram (-)-NA/h. Infusion of 1 microgram (-)-NA/h to control rats did not cause any change, while infusion of 5 microgram (-)NA/h led to a significant decrease (-24%) in 3]DHA binding. The present results further support the view that the availability of NA at the receptors controls the number of beta-adrenergic receptors, thereby probably regulating the NA sensitivity of cells with beta-receptors.