Pergolide inhibition of calcium-induced /sup 3/H-dopamine release from striatal synaptosomes

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6846473

Bowyer, J F; Weiner, N

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-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

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550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMISTRY
CALCIUM COMPOUNDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CATIONS
CHARGED PARTICLES
CHEMISTRY
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HYDROXY COMPOUNDS
INHIBITION
IONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVE CELLS
NEUROREGULATORS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
RATS
RECEPTORS
RODENTS
SECRETION
SOMATIC CELLS
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES