Abstract
In order to investigate supersensitization induced by guanethidine, the effect of guanethidine on the dose-response curves to norepinephrine and other agonists (acetylcholine and histamine) was examined using the vas deferens of guinea pigs. The degree of supersensitivity to norepinephrine was dose-dependent (3×10-5M to 1×10-6M guanethidine) and the maximum degree was almost the same as that induced by cocaine. Guanethidine did not increase the maximum response to norepinephrine. In the presence of a low concentration of cocaine, guanethidine induced a further potentiation of the response to norepinephrine ; the maximum potentiation induced by the added guanethidine was almost the same as that induced by a high concentration of cocaine or guanethidine alone. In the presence of high cocaine concentration which produced nearly maximal potentiation, addition of guanethidine did not induce further potentiation. The concentration of guanethidine required to block the sympathetic nerve was lower than that required to potentiate norepinephrine. 3×10-5M and 1×10-4M guanethidine increased the response to acetylcholine and histamine. Supersensitivity to acetylcholine produced by guanethidine was dose-dependent and guanethidine (1×10-4M) induced a slight increase in the maximum response to histamine. These results suggest that guanethidine induces supersensitization to norepinephrine to the same degree as cocaine, and induces a so-called "non-specific supersensitization"to acetylcholine and histamine.
