Relaxant effects of aflatoxins on isolated guinea pig trachea

Dyspnea is one of the symptoms of acute aflatoxicosis. Contrary to expectat ions, 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 d ifferent degrees. The efficacies but not the potencies of AFB(1), AFB(2), A FG(1), and AFG(2) were similar to that of the P-agonist, isoprenaline, whos e activity was potentiated by the AF. Their mechanism of action is not clea rly understood but several mechanistic indications were obtained with AFB(1 ): 1) its effect was not influenced by the beta-blocker, timolol, indicatin g that a direct interaction with beta(2)-adrenergic receptors was not invol ved. 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 guin ea pig trachea relaxed by AFB(1) increased, possibly due to inhibition of p hosphodiesterase; direct interaction with PC 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 relaxan t activity of AFB(1), it is speculated that this mycotoxin could stimulate inhibitory nonadrenergic, noncholinergic nerves (I-NANC). In conclusion, th e symptoms of acute aflatoxicosis do not seem to be due to a direct activit y on the tracheal muscle, but rather, to the well-known pro-inflammatory ac tivity of the aflatoxins, which are capable of releasing arachidonic acid f rom cell membranes.