Maitotoxin-induced calcium entry in human lymphocytes: modulation by yessotoxin, Ca(2+) channel blockers and kinases.

Abstract

We have studied the effect of the ciguatera-related toxin maitotoxin (MTX) on the cytosolic free calcium concentration ([Ca(2+)]i) of human peripheral blood lymphocytes loaded with the fluorescent probe Fura2 and the regulation of MTX action by different drugs known to interfere in cellular Ca(2+) signalling mechanisms and by the marine phycotoxin yessotoxin (YTX). MTX produced a concentration-dependent elevation of [Ca(2+)]i in a Ca(2+)-containing medium. This effect was stimulated by pretreatment with YTX 1 microM and NiCl(2) 15 microM. The voltage-independent Ca(2+) channel antagonist 1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenyl]-1H-imidazole hydrochloride (SKF96365) blocked the MTX-induced [Ca(2+)]i elevation, while the L-type channel blocker nifedipine had no effect. Pretreatment with NiCl(2) or nifedipine did not modify YTX-induced potentiation of MTX effect, and SKF96365-induced inhibition was reduced in the presence of YTX, which suggest different pathways to act on [Ca(2+)]i. Preincubation with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide.2HCl (H-89) or genistein (10 microM) also had no effect on the MTX-induced [Ca(2+)]i increment. In contrast, the PKC inhibitor bisindolilmaleimide I (GF109203X 1 microM) potentiated the MTX effect, whereas phosphatidylinositol (PI) 3-kinase inhibition with wortmannin (10 nM) reduced the MTX-elicited Ca(2+) entry. In summary, MTX produced Ca(2+) influx into human lymphocytes through a SKF96365-sensitive, nifedipine-insensitive pathway. The MTX-induced [Ca(2+)]i elevation was stimulated by the marine toxin YTX through a mechanism insensitive to SKF96365, nifedipine or NiCl(2). It was also stimulated by the divalent cation Ni(2+) and PKC inhibition and was partially inhibited by PI 3-kinase inhibition.

• Authors: L A de la Rosa, A Alfonso, N Vilariño, M R Vieytes, T Yasumoto, L M Botana
• Journal: Cellular signalling (Cell Signal) Vol. 13 Issue 10 Pg. 711-6 (Oct 2001) ISSN: 0898-6568 [Print] England
• PMID: 11602181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Enzyme Inhibitors
• Ethers, Cyclic
• Imidazoles
• Marine Toxins
• Mollusk Venoms
• Oxocins
• nickel chloride
• Nickel
• maitotoxin
• Phosphotransferases
• 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
• Nifedipine
• yessotoxin
• Calcium

Topics

• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Cells, Cultured
• Drug Interactions
• Enzyme Inhibitors (pharmacology)
• Ethers, Cyclic (pharmacology)
• Humans
• Imidazoles (pharmacology)
• Kinetics
• Lymphocytes (drug effects, metabolism)
• Marine Toxins (pharmacology)
• Mollusk Venoms
• Nickel (pharmacology)
• Nifedipine (pharmacology)
• Oxocins
• Phosphotransferases (antagonists & inhibitors)