NEUROPEPTIDE-DOPAMINE INTERACTIONS .5. CYCLO(HIS-PRO) REGULATION OF STRIATAL DOPAMINE TRANSPORTER COMPLEX

被引:36
作者
IKEGAMI, H
PRASAD, C
机构
[1] LOUISIANA STATE UNIV, MED CTR,DEPT MED,ENDOCRINOL SECT,1542 TULANE AVE, NEW ORLEANS, LA 70112 USA
[2] PENNINGTON BIOMED RES CTR, NEUROSCI LAB, BATON ROUGE, LA USA
关键词
Cyclo(His-Pro); D[!sub]1[!/sub]-DA receptor; D[!sub]2[!/sub]-DA receptor; DA transporter complex; DA uptake; Mazindol-binding sites;
D O I
10.1016/0196-9781(90)90123-M
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclo(His-Pro) (CHP) is a cyclic dipeptide that is ubiquitously distributed through the central nervous system, including striatum. Many biologic effects of CHP seem to be mediated through a dopaminergic mechanism. To further examine the mechanism of action of this peptide, we have studied effects of chronic CHP treatment on the properties of nigro-striatal dopaminergic neurons in rats. Chronic CHP administration elicited significant increase in both KD and Bmax of striatal mazindol-binding sites (labelling DA transporter complex), but no change in either D1- or D2-type DA receptors. Chronic treatment with DA uptake blockers (e.g., benztropine, GBR 12909, bupropion, and mazindol) also produced changes in striatal mazindol-binding sites that were similar to that of chronic CHP. Furthermore, CHP led to a dose-dependent inhibition of [3H]-DA uptake by striatal synaptosomes, reaching to maximal inhibition of uptake (30%) at CHP dosage of 10 nM. The dose-response curve for CHP inhibition of DA uptake, unlike DA uptake blockers that led to a total inhibition, was partial and V-shaped. Again unlike DA uptake blockers, CHP did not inhibit the binding of [3H]-mazindol to striatal membranes. On the basis of these data we hypothesize that while CHP may inhibit DA uptake by modifying mazindol-binding locus at DA transporter complex, its primary action may be at a site other than mazindol-binding site. © 1990.
引用
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页码:145 / 148
页数:4
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