Mechanism of cardiotoxicity induced by a marine toxin isolated from Ptychodiscus brevis.
An organophosphate toxin of marine origin isolated from red tide dinoflagellate P. brevis produced a dose-dependent dual effect on rat atria, i.e. positive inotropic effect at low concentrations (2.8 x 10(-8) to 8.4 x 10(-7) M) and negative inotropic and chronotropic responses at an elevated dose (4.8 x 10(-6) to 7.2 x 10(-4) M). The negative chronotropic and inotropic responses of the toxin were potentiated with physostigmine and ouabain whereas antagonized by atropine and hemicholinium-3 pretreatments and those effects remained unaltered by isoproterenol, phenylephrine and ouabain pretreatments. The results indicate that the toxin induced negative inotropic and chronotropic effects are mediated through release of acetylcholine from the nerve endings and consequent activation of muscarinic receptor. In atria exposed to guanethidine, bretylium, propranolol and tyramine tachyphylaxis, the positive inotropic response of the toxin was not modified. However, the response was antagonized by EGTA, nifedipine, ryanodine, calcium-free ringer and potentiated with caffeine and amiloride pretreatments. The results suggest that the positive inotropic effect of the toxin is mediated through Ca2+ influx and impairment of Na+/Ca2+ exchange process.
Mazumder
P K
PK
Division of Pharmacology & Toxicology, Defence Research and Development Establishment, Gwalior, India.
Gupta
A K
AK
Kumar
D
D
Kaushik
M P
MP
Dube
S N
SN
D000818:Animals; D004141:Dinoflagellida / Q000737:chemistry*; D006325:Heart Atria / Q000187:drug effects*; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D008387:Marine Toxins; D009943:Organophosphorus Compounds