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

Eur J Pharmacol. 1981 Jan 29;69(3):341-6. doi: 10.1016/0014-2999(81)90480-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Denervation
  • Hydroxydopamines / administration & dosage
  • Hydroxydopamines / pharmacology
  • Injections, Intraventricular
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology*
  • Rats
  • Receptors, Adrenergic / metabolism*
  • Receptors, Adrenergic, beta / metabolism*

Substances

  • Hydroxydopamines
  • Receptors, Adrenergic
  • Receptors, Adrenergic, beta
  • Norepinephrine