Relaxant effects of aflatoxins on isolated guinea pig trachea.
Dyspnea is one of the symptoms of acute aflatoxicosis. Contrary to expectations, we observed that naturally occurring aflatoxins (AF) AFB(1), AFB(2), AFG(1), and AFG(2) and their major metabolites AFM(1), AFM(2), AFP(1), AFQ(1), and AFG(2a) relaxed carbachol (C) precontracted guinea pig trachea to different degrees. The efficacies but not the potencies of AFB(1), AFB(2), AFG(1), and AFG(2) were similar to that of the beta-agonist, isoprenaline, whose activity was potentiated by the AF. Their mechanism of action is not clearly understood but several mechanistic indications were obtained with AFB(1): 1) its effect was not influenced by the beta-blocker, timolol, indicating that a direct interaction with beta(2)-adrenergic receptors was not involved. 2) AFB(1) potentiated PGE(1) and PGE(2), two relaxant prostaglandins, and its activity was reduced by indomethacin. 3) The cAMP level in the guinea pig trachea relaxed by AFB(1) increased, possibly due to inhibition of phosphodiesterase; direct interaction with PG receptors; and/or interaction with A(2) adenosinic receptors, suggested by the inhibitory activity of XAC, a specific antagonist. 4) Finally, since tetrodotoxin reduced the relaxant activity of AFB(1), it is speculated that this mycotoxin could stimulate inhibitory nonadrenergic, noncholinergic nerves (i-NANC). In conclusion, the symptoms of acute aflatoxicosis do not seem to be due to a direct activity on the tracheal muscle, but rather, to the well-known pro-inflammatory activity of the aflatoxins, which are capable of releasing arachidonic acid from cell membranes.
Abdel-Haq
H
H
Department of Pharmacology of Natural Substances and General Physiology, University of Rome La Sapienza, Rome, Italy.
Palmery
M
M
Leone
M G
MG
Saso
L
L
Silvestrini
B
B
D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D011453:Prostaglandins / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000294:innervation
D000348:Aflatoxins; D001993:Bronchodilator Agents; D002273:Carcinogens; D018721:Muscarinic Agonists; D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D018047:Receptors, Purinergic P1; D013779:Tetrodotoxin; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol