Contractions induced by grayanotoxin I in the guinea-pig vas deferens

1 In the guinea-pig vas deferens, grayanotoxin I (G-I), a diterpenic toxin isolated from certain ericaceous plants caused rhythmic contractions which were dose-dependent (5 x 10(-5) M - 10(-3) M); these followed an initial transient contraction.2 The G-I (3 x 10(-4) M)-induced contraction was markedly inhibited or abolished by reserpine (2 mg/kg on 2 days), phentolamine (2 x 10(-7) M and 10(-6) M) or tetrodotoxin (TTX, 5 x 10(-7) M), but remained almost unaffected by atropine (10(-6) M) or mecamylamine (3 x 10(-5) M). This contraction was also abolished after storage at 4 degrees C for 7 days or incubation in Na-deficient or Ca-free medium.3 After treatment with G-I (3 x 10(-5) M), which did not alter the tension of the preparation, transmural stimulation (10-50 Hz, 0.5 ms, supramaximal voltage, for 3 s) induced a slower contraction (second contraction) following the first rapid contraction caused by stimulation.4 The second contraction was inhibited or abolished by reserpine (2 mg/kg on 2 days), phentolamine (2 x 10(-7) M and 10(-6) M) and TTX (2 x 10(-8) M), but was not affected by atropine (10(-6) M) and mecamylamine (3 x 10(-5) M).5 G-I (3 x 10(-5) M) shifted the dose-response curves for noradrenaline (NA), acetylcholine and high-K contractions to the left in a parallel manner and slightly increased the maximal response to these agonists.6 G-I (3 x 10(-4) M) caused a release of endogenous NA from the vas deferens which was approximately 120 times that of control preparations. This response was inhibited or abolished by TTX (5 x 10(-7) M) or incubation in Ca-free medium.7 These results suggest that the G-I-induced contraction of the vas deferens and the G-I-induced second contraction on electrical stimulation are the result of an indirect action mediated through the release of NA from the adrenergic nerve endings.