These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pardaxin induces exocytosis in bovine adrenal medullary chromaffin cells independent of calcium.
    Author: Lazarovici P, Lelkes PI.
    Journal: J Pharmacol Exp Ther; 1992 Dec; 263(3):1317-26. PubMed ID: 1469638.
    Abstract:
    Pardaxin, an excitatory neurotoxin, is a new tool for studying the machinery of neurotransmitter secretion. At noncytotoxic concentrations (< 1 x 10(-5) M), pardaxin stimulated exocytosis, as assessed by the concomitant release of catecholamines, ATP and dopamine-beta-hydroxylase from bovine adrenal medullary chromaffin cells in the presence or absence of extracellular calcium. At higher concentrations (> 2 x 10(-5) M), pardaxin was increasingly cytotoxic, as inferred from trypan blue uptake, release of lactate dehydrogenase and 51Cr (ED50 = 100 microM). The role of intracellular calcium ([Ca++]i) homeostasis in pardaxin action was investigated by using the fluorescent calcium indicator Fura-2. In the presence of extracellular calcium, addition of noncytotoxic concentrations of pardaxin yielded a steady, concentration-dependent rise in [Ca++]i (ED50 = 1 microM). Depolarization of chromaffin cells by high K+ reduced pardaxin binding and abolished the pardaxin-evoked rise in [Ca++]i. In the absence of extracellular calcium, pardaxin failed to elicit an elevation of [Ca++]i. These data suggest that, in the presence of extracellular calcium, pardaxin might cause elevations in [Ca++]i and neurotransmitter release, concomitant with inducing transmembranal Ca++ influx. However, the complex concentration dependence of [Ca++]i and the fact that pardaxin stimulated secretion without a rise of [Ca++]i suggest that the toxin, in addition to being a pore-forming molecule, might directly affect exocytosis in a Ca(++)-independent way. In proposing a pharmacological working model, we hypothesize that pardaxin might present a molecular structure which mimics an essential step in the endogenous docking mechanism between secretory granules and the plasma membrane.
    [Abstract] [Full Text] [Related] [New Search]