Characterization of pardaxin-induced dopamine release from pheochromocytoma cells: Role of calcium and eicosanoids

Saleh Abu-Raya, Eugenia Bloch-Shilderman, Peter I. Lelkes, Victoria Trembovler, Esther Shohami, Yehuda Gutman, Philip Lazarovici*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Pardaxin, an excitatory neurotoxin, induced dopamine release from pheochromocytoma (PC12) cells both in the presence and absence of extracellular calcium ([Ca](o)). In the presence of extracellular calcium, nifedipine, an L-type calcium channel blocker, did not affect dopamine release, whereas 1,2-bis (2-aminophenoxy) ethane N,N, N'N'-tetra-acetic acid (BAPTA), a chelator of cytosolic calcium, and dantrolene, a blocker of calcium release from intracellular stores, inhibited only partially (30-40%) pardaxin-induced dopamine release. In the absence of [Ca](o), BAPTA and dantrolene were ineffective. Pardaxin stimulated the arachidonic acid (AA) cascade in PC12 cells independently of [Ca](o). The phospholipase inhibitors mepacrine and bromophenacyl bromide inhibited both pardaxin-induced AA release and pardaxin-induced dopamine release. Dopamine release induced by pardaxin also was blocked by the lipoxygenase inhibitors nordihydroguaiaretic acid, esculetin, and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4- benzoquinone. Under these conditions, a parallel reduction in 5- hydroxyeicosatetranoic acid release also was observed. Suppression of pardaxin-induced dopamine release by inhibitors of phospholipase A2 and lipoxygenase was more pronounced in calcium-free medium. These results indicate the involvement of the lipoxygenase pathway in pardaxin-induced dopamine release and suggest the use of this toxin as a novel pharmacological tool for investigating the mechanism of calcium-independent neurotransmitter release.

Original languageEnglish
Pages (from-to)399-406
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume288
Issue number2
StatePublished - Feb 1999

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