REGULATION OF DOPAMINE RECEPTOR SUBTYPES

Project Details

Description

Studies of dopamine receptors had established that two pharmacologically
distinct subtypes of dopamine receptors are expressed in the CNS, D1 and
D2 receptors. Recent molecular genetic studies have now identified at
least five distinct genes that codes for members of the family of G
protein-coupled receptors that are activated by dopamine. The products
for these genes possess pharmacologic properties similar to either D1 or
D2. The genes for D1a and D1b receptors have been cloned and sequenced.
These two receptors have been shown to share structural and pharmacologic
properties. Studies on the in vivo regulation of dopamine receptors have
thus far focused on D1 and D2 receptors because of the availability of
high-affinity antagonists that can be used to differentiate between D1
and D2 and because these two dopamine receptor subtypes are expressed
with the highest receptor density. Studies on the regulation of the
other dopamine receptor subtypes are hampered by the lack of regents that
can be used to selectively quantitate the expression of these receptor
subtypes. This proposal describes experiments designed to develop
receptor specific polyclonal and monoclonal antibodies and riboprobes
that can be used to quantitatively measure the expression of the rat D1-
like dopamine receptor subtypes D1a and D1b and the mRNA coding for these
receptors. Receptor specific reagents will be used to determine
relationship between dopamine receptors in the brain and in the
periphery, for receptor purification studies to investigate how
antagonists bind to dopamine receptors, and to define how the
administration of antipsychotic and antihypertensive drugs influence the
in vivo expression of D1a and D1b receptors and receptor mRNA. A
solution hybridization/ribonuclease protection assay and immunological
techniques will be used to quantitate the levels of receptor mRNA and the
expression of receptors, respectively.
StatusFinished
Effective start/end date1/01/9331/12/93