Pergolide inhibition of calcium-induced /sup 3/H-dopamine release from striatal synaptosomes
Several investigators have reported that dopamine agonists or antagonists are unable to modulate the K/sup +/-evoked release of /sup 3/H-dopamine (/sup 3/H-DA) from striatal synaptosomes. To further assess the role of DA in regulating its release, they have examined the effects of pergolide on Ca/sup + +/ (1.25 mM)-evoked release of /sup 3/H-DA from partially K/sup +/-depolarized striatal synaptosomes. Synaptosomes (P2 pellet) were isolated from rat striatum and incubated for 5 min at 37/sup 0/C in a Ca/sup + +/-free Krebs-Ringer buffer containing 25 nM /sup 3/H-DA. After radiolabeling, the synaptosomes were superfused for 12 min with Ca/sup + +/-free 6 mM Krebs-Ringer buffer to determine basal release of /sup 3/H-DA. Synaptosomes were then exposed to test drugs for 8 min prior to Ca/sup + +/ challenge. Ca/sup + +/ addition resulted in a 3-fold increase in /sup 3/H-DA release within 2-4 min. Pergolide inhibited the release of /sup 3/H-DA in a concentration-dependent manner. Release was inhibited to 56% of control by 10 nM pergolide. This was largely reversed by 0.1 ..mu..M S-sulpiride. Ca/sup + +/-evoked release was inhibited over 70% by 1 ..mu..M tetrodotoxin (TTX), indicating that voltage-dependent Na/sup +/ channels may play a role in the release process. The combination of pergolide and TTX inhibited release to a degree similar to TTX alone. These results suggest that pergolide may inhibit /sup 3/H-DA release by a TTX-sensitive mechanism and that the dopaminergic autoreceptors may be linked to voltage-sensitive Na/sup +/ channels.
- Research Organization:
- Univ. of Colorado School of Medicine, Denver
- OSTI ID:
- 6846473
- Report Number(s):
- CONF-8604222-; TRN: 87-008606
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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