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.
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003714:Denervation; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine