Differential effects of maitotoxin on ATP secretion and on phosphoinositide breakdown in rat pheochromocytoma cells

Abstract

Maitotoxin (MTX) induced exocytotic secretion of ATP from PCI2 rat pheochromocytoma cells. The threshold for stimulation of secretion was at concentrations of about 2 ng/ml of MTX. Maximal release occurred at 40 ng/ml. MTX-induced ATP release required the presence of calcium in the extracellular medium and could be inhibited by nifedipine, a specific blocker of voltage-dependent calcium channels. In addition to the effects on ATP secretion from PCI2 cells, MTX stimulated the breakdown of phosphoinositides, as measured by the accumulation of rH]inositol phosphates. Maximal stimulation of phosphoinositide breakdown was reached at only 0.5-1.0 ng/ml MTX. MTX at concentrations required to evoke ATP release (> 2 ng/ml) had lesser or no effect on phosphoinositide breakdown. Although stimulation of phosphoinositide breakdown by MTX was dependent on extracellular calcium, it was insensitive to the calcium channel blockers nifedipine, D-600 and cobalt ions. The different concentration range required to elicit these responses and the varying sensitivity to calcium channel blockers indicate that MTX-evoked secretion and MTX-stimulated phosphoinositide breakdown are independent phenomena in PC I2 cells.ATP secretion; Phosphoinositide breakdown; Maitotoxin; (PC 12 cell)

Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function

“…From these results it was concluded that both P-CTX-1 and bradykinin might elevate intracellular Ca 2+ through the same InsP 3 -sensitive Ca 2+ stores in nerve cells [ 104 ]. Past experimentation on synaptosomes [ 160 – 162 ] and cardiac myocytes [ 163 ] has also revealed that any enhanced influx of Na + stimulates the production of InsP 3 , presumably through the activation of phospholipase C. A Na + -dependent mobilization of Ca 2+ from InsP 3 -sensitive stores could explain the increase in asynchronous quantal neurotransmitter release from motor nerve terminals that have been exposed to P-CTX-1 in a Ca 2+ -free bath solution [ 103 , 106 ]. More recently P-CTX-1 has been shown to cause a transient increase in intracellular InsP 3 mass levels in rat myotubes, an action that was blocked by TTX [ 142 ].…”

Purinergic Signaling in the Hallmarks of Cancer

“…Extracellular ATP (exATP) and exADO are accepted biochemical markers of cancer, due to their significant levels in the tumor interstitium. ATP release by cancer cells and the subsequent activation of purinergic receptors and intracellular pathways have been reported in various cancer models, such as pheochromocytoma PC-12 cells stimulated with maitotoxin [13]; Ehrlich ascites tumor cells, ATP release induced by mechanical stimulation [14]; A549 human lung cancer cells, by exocytosis triggered by TGF-β stimulation [15]; SKOV-3 ovarian carcinoma-derived cells released by a pipette generated flux [16]; I-10 testicular cancer cells through pannexin-1 [17]. A breakthrough was the monitoring of ATP in vivo in a tumor-bearing mouse with the use of reporter cells carrying an extracellular ATP sensor.…”

Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates

“…MTX is believed to be a powerful disruptor of Ca 2+ homeostasis, with a multiplicity of pharmacological effects upon several cell lines [ 119 ]. Its ability to trigger intracellular cascades of events—e.g., membrane depolarization in excitable cells [ 126 ], insulin [ 127 ] and neurotransmitter secretion [ 128 , 129 ], phosphounisitide breakdown (important in cell lipids and cell signaling) [ 130 ], programmed cell death [ 131 ], and fertilization [ 132 , 133 ], justify why this compound is a powerful tool for research in cell biology, namely when attempting to elucidate Ca 2+ -dependent cellular processes [ 119 ]. MTX has also been suggested to play a role in innate immune responses and inflammation in vivo [ 119 , 134 ].…”