Dopamine agonist-mediated inhibition of acetylcholine release in rat striatum is modified by thyroid hormone status.
K(+)-evoked acetyl[3H]choline ([3H]ACh) release was inhibited in a concentration-dependent manner by apomorphine and the D2 agonist quinpirole in striatal slices prepared from euthyroid and hypothyroid rats. However, there was a significant increase in the maximum inhibition observed 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 [3H]ACh release by apomorphine, confirming an inhibitory role for D2 receptors and 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 receptor sensitivity affects a receptor-mediated event. Following intrastriatal injection of pertussis toxin (PTX), apomorphine no longer inhibited [3H]ACh release. In fact, increased [3H]-ACh release was observed, an effect reduced by SCH 23390, providing evidence that D1 receptors enhance [3H]-ACh release, and confirming that a PTX-sensitive G protein mediates the D2 response. As it has been reported that thyroid hormones modulate G protein expression, this mechanism may underlie their effect on dopamine agonist-mediated inhibition of ACh.
Foley
P B
PB
Department of Clinical Pharmacology, Flinders University of South Australia, Adelaide.
Crocker
A D
AD
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D013963:Thyroid Hormones; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D000109:Acetylcholine