Prejunctional supersensitization of adrenergic transmission of the isolated guinea pig vas deferens produced by an atoxic fraction from scorpion venom (Tityus serrulatus).

The effects of four atoxic fractions prepared from Tityus serrulatus venom on the response of isolated guinea pig vas deferens to norepinephrine (NE) and acetylcholine (Ach) were studied. The fractions, prepared by gel filtration on Sephadex G-50, did not contain Tityustoxin (TsTX) and were used in the concentration range 20-40 micrograms/ml tissue bath. Fraction III decreased the ED50 of NE 7.1-fold (P less than 0.01) and of Ach 17.8-fold (P less than 0.01) but did not significantly modify the maximal response (MR) to either agonist. The other fractions had much less pronounced effects, if any, on the ED50 and/or MR of either Ach or NE. The effect of Fraction III on responsiveness to NE was not demonstrable on vas deferens of pharmacologically "denervated" animals (pretreated with reserpine and alpha-methyl-p-tyrosine) but was demonstrable in tissue from normal animals tested in the presence of atropine. The effect of Fraction III on responsiveness to Ach was abolished by the presence of phentolamine in the tissue bath. These data indicate that Fraction III induces a prejunctional type of supersensitivity by acting mainly on adrenergic transmission and suggest that it may be a useful tool for the investigation of the mechanism of action of drugs that act on nerve terminals.