Dual actions of (-)-stepholidine on dopamine receptor subtypes after substantia nigra lesion.
1. It was found that the contralateral rotation challenged by (-)-SPD (4 mg/kg, ip) in 6-OHDA-lesioned rats had a gradually progressive process with long latent period and a maximal response on 63 days after lesion. This steady contralateral rotation was preferably antagonized by D-1 antagonist SCH23390 than D-2 antagonists. During its latent period (-)-SPD exhibited the antagonistic effect to APO, while during its period of full response (-)-SPD could potentiate the APO-induced rotation. 2. In the rats lesioned with kainic acid plus 6-OHDA to destroy the SNC and SNR, (-)-SPD and SKF-38393 challenged neither contralateral nor ipsilateral rotation, while APO still induced the rotation but towards ipsilateral side, just opposite to that in 6-OHDA-lesioned rats. In this case, (-)-SPD antagonized the response to APO as did SCH 23390. 3. These evidences suggest that the agonistic action of (-)-SPD is resulted from D-1 receptor subtype at the SNR under supersensitive functional state. The fact that SNR lesion could completely eliminate the agonistic action of (-)-SPD further indicate that the D-1 receptors in the ipsilateral SNR may be the sites of action of (-)-SPD. The dual actions of (-)-SPD are dependent upon the supersensitivity of D-1 receptor subtypes which render the antagonistic action to convert into the agonistic.
Institute of Materia Medica, Academia Sinica, Shanghai, People's Republic of China.
G Z
GZ
Jin
K X
KX
Huang
B C
BC
Sun
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects*; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D001599:Berberine; C010513:stepholidine; C047508:rotigotine; D016627:Oxidopamine; D001058:Apomorphine