AUTORADIOGRAPHIC STUDIES OF THE REGULATION OF THE SUBTYPES OF THE ß ADRENERGIC RECEPTOR

The regulation of the subtypes of the ß adrenergic receptor following a number of treatment regimens was examined. Following a generalized catecholaminergic intraventricular innervation administration to of the lesion rat of CNS the by the compound 6-hydroxydopamine (6-0HDA) to adult rats, both subtypes of the ß adrenergic receptor were shown to increase in density in a number of anatomically discrete brain regions. There are brain regions where both subtypes increased in density, regions where only one subtype increased in density and regions where neither subtype changed. When the compound 6-0HDA is administered to neonatal rat pups on the first four days of life, a more selective lesion of the noradrenergic innervation results. Again, both subtypes of the ß adrenergic receptor increased in density in a number of brain regions. The density of ß-1 adrenergic receptors in the caudate-putamen increased after this treatment. The density of ß-1 receptors did not change in the caudate-putamen following the nonselective lesion. A selective lesion of the dopaminergic input to the caudate-putamen resulted in a decrease in the density of ß-1 adrenergic receptors there. The density of ß-2 adrenergic receptors did not change following this lesion. Chronic administration of the tricyclic antidepressant desmethylimipramine (DMI) resulted in the down regulation of ß-1 adrenergic receptors in most brain regions. ß-2 Adrenergic receptor density was unchanged in any brain region studied. From the observation of how the subtypes of the ß adrenergic receptor change following the different treatment regimens, the following conclusions can be made: 1. Both subtypes of the ß adrenergic receptor are heterogeneously distributed in the rat CNS. 2. ß-2 adrenergic receptors in a least some brain regions appear to be innervated. 3. ß-1 and ß-2 adrenergic receptor densities are independently regulated. Changes in the density of one subtype in a particular region are independent of what happens to the density of the other subtype in that area. 4. A subpopulation of ß-l adrenergic receptors in the caudate-putamen appear to be associated with dopaminergic neurons. Destruction of the dopaminergic innervation results in a loss of ß-l receptors. The change in the density of both subtypes of the ß adrenergic receptor in various regions of the rat brain in response to both increases and decreases in the noradrenergic tone are good indications that there is a functional noradrenergic innervation of both subtypes. These results indicate that ß-2 adrenergic receptors may play a more important role in noradrenergic function in the CNS than previously thought

Author dc:creator

• Eric W. Johnson

Advisors dc:contributor.advisor

• Molinoff, Perry
• Wolfe, Barry

• Pharmacology, Toxicology and Environmental Health

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/61521

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/61521