Pb. Foley et Ad. Crocker, DOPAMINE AGONIST-MEDIATED INHIBITION OF ACETYLCHOLINE-RELEASE IN RAT STRIATUM IS MODIFIED BY THYROID-HORMONE STATUS, Journal of neurochemistry, 61(3), 1993, pp. 812-817
K+-evoked acetyl[H-3]choline ([H-3]ACh) release was inhibited in a con
centration-dependent manner by apomorphine and the D2 agonist quinpiro
le in striatal slices prepared from euthyroid and hypothyroid rats. Ho
wever, there was a significant increase in the maximum inhibition obse
rved with both agonists in the hypothyroid compared with the euthyroid
group, which paralleled the increased D2 agonist sensitivity reported
for stereotyped behavior. The D2 antagonist raclopride decreased, and
the D1 antagonist SCH 23390 increased, the inhibition of [H-3]ACh rel
ease by apomorphine, confirming an inhibitory role for D2 receptors an
d an opposing role for D1 receptors. Because there is no difference in
D1 or D2 receptor concentration between the euthyroid and hypothyroid
groups, it is suggested that thyroid hormone modulation of D2 recepto
r sensitivity affects a receptor-mediated event. Following intrastriat
al injection of pertussis toxin (PTX), apomorphine no longer inhibited
[H-3]ACh release. In fact, increased [H-3]ACh release was observed, a
n effect reduced by SCH 23390, providing evidence that D1 receptors en
hance [H-3]ACh release, and confirming that a PTX-sensitive G protein
mediates the D2 response. As it has been reported that thyroid hormone
s modulate G protein expression, this mechanism may underlie their eff
ect on dopamine agonist-mediated inhibition of ACh.