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 × 10^-5 M — 10^-3 M); these followed an initial transient contraction.

2 The G-I (3 × 10^-4 M)-induced contraction was markedly inhibited or abolished by reserpine (2 mg/kg on 2 days), phentolamine (2 × 10^-7 M and 10^-6 M) or tetrodotoxin (TTX, 5 × 10^-7 M), but remained almost unaffected by atropine (10^-6 M) or mecamylamine (3 × 10^-5 M). This contraction was also abolished after storage at 4°C for 7 days or incubation in Na-deficient or Ca-free medium.

3 After treatment with G-I (3 × 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 × 10^-7 M and 10^-6 M) and TTX (2 × 10^-8 M), but was not affected by atropine (10^-6 M) and mecamylamine (3 × 10^-5 M).

5 G-I (3 × 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 × 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 × 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.

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