Comparison of (-)-stepholidine and D1 or D2 agonists on unit firing of globus pallidus in 6-hydroxydopamine-lesioned rats.
(-)-Stepholidine(SPD), isolated from the Chinese herb Stephania, is demonstrated to be a DA antagonist, but it also shows D1 agonistic action on rotational behavior in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. The present study further ascertains its D1 agonistic property on firing activity of globus pallidus (GP) in control and 6-OHDA-lesioned rats. In the control rats, the firing activities of the GP neurons elicited by DA agonists (i.v.), such as apomorphine (D1/D2), SKF38393 (D1), and LY171555 (D2), were readily reversed by SPD (4 mg/kg, i.v.); but SPD, per se, induced variable alterations. In the 6-OHDA-lesioned rats, apomorphine, SKF38393 and LY171555 displayed the marked inhibition as well as excitation on the unit firing. The individual firing variations (87.1+/-17.8, 55.1+/-15.7 and 62.1+/-16.7%, respectively) were much larger than those in the control group, and were completely abolished by SPD (2 mg/kg). However, SPD also showed D1 partial agonistic action on the GP neuron firing. Moreover, the pre-blockade of D2 receptors with spiperone (0.5 mg/kg, i.v.), SPD exhibited the D1 agonist action which was reversed by the D1 antagonist SCH23390. These results suggest that SPD has a dual action on the GP neuron firing in the 6-OHDA-lesioned rats, i.e., antagonist to D2 DA receptors and partial agonist to D1 receptors.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, PR China.
X X
XX
Zhang
Z T
ZT
Zhu
G Z
GZ
Jin
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004347:Drug Interactions; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists*
D001552:Benzazepines; D002121:Calcium Channel Blockers; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001599:Berberine; C010513:stepholidine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine