Acute effects of aflatoxins on guinea pig isolated ileum.
Previous studies on the aflatoxins have focused mainly on their chronic toxic effects. In this study we investigated the acute gastrointestinal effects of four common aflatoxins on isolated guinea pig ileum. AFB(1) (EC(50) 4.6+/-0.4 microM) and AFB(2) (EC(50)17+/-4.4 microM) contracted isolated guinea pig ileum in a dose-dependent manner, whereas AFG(1) and AFG(2) evoked no contractions. Atropine (5.9 nM 11.8 and 23.6 nM) antagonized AFB(1)-induced contractions in a dose-dependent manner. Pretreatment with the nicotinic ganglionic blocker, hexamethonium (up to 55 microM), left AFB(1)-induced contractions unchanged. In contrast, tetrodotoxin (0.3 microM), blocked AFB(1) contractile activity. The two inhibitors of ACh release, morphine (0.3 microM) and clonidine (0.4 microM), antagonized EC(50) AFB(1)-induced contractions, and apamin, a drug that increases neuronal excitability, facilitated the EC(50) AFB(1)-induced contractile effect. The choline uptake blocker, hemicholinium (17.4 microM) markedly reduced AFB(1)-induced contractions. These results suggest that aflatoxins induce their contractile effect indirectly through the cholinergic system by stimulating acetylcholine release from the postganglionic parasympathetic nerve endings. The acute actions of aflatoxins on isolated guinea pig ileum could explain their acute gastrointestinal effects in humans and animals.
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Department of Pharmacology of Natural Substances and General Physiology, University of Rome La Sapienza, P. le A. Moro 5, 00185 Rome, Italy.
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D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology
D000348:Aflatoxins; D001030:Apamin; D018738:Hexamethonium; D013779:Tetrodotoxin; D009020:Morphine; D001285:Atropine; D003000:Clonidine