Endogenous modulator of dopamine receptor(s).
An endogenous modulator(s) of the dopamine receptor(s) in bovine and rat brain striatum was detected by demonstrating that water extracts of the striatum inhibited [(3)H]apomorphine binding. This modulator(s) was partially purified by methanol extraction and then successive ion exchange chromatographies on SP-Sephadex C-25 and QAE-Sephadex A-25, and gel chromatography on Sephadex G-25. The partially purified (about 1,500-fold) modulator was a fluorescamine-positive substance, Mr = 500 1000, which was heat-stable (95 degrees C, 10 min), and was destroyed by acid- and alkali-treatment, but not by treatments with various peptidases. The modulator inhibited binding of the dopamine agonist, [(3)H]apomorphine non-competitively, but did not inhibit binding of the dopamine antagonist, [(3)H]spiroperidol. Direct injection of the modulator into rat brain striatum depressed apomorphine-induced locomotor activity. Moreover the modulator inhibited dopamine-sensitive adenylate cyclase activity. These findings indicate that the modulator acts at a site(s) other than the ligand binding site of the dopamine receptor(s) and modulates the activities of dopamine agonists.
Hirata
A
A
Department of Pharmacology I, Osaka University School of Medicine, Osaka 530, Japan.
Yamada
I
I
Fujita
N
N
Saito
K
K
Nakahiro
M
M
Yoshida
H
H