Study of the mechanism of the relaxant action of (+)‐glaucine in rat vas deferens

1 Effects of the aporphinoid alkaloid, (+)‐glaucine, on rat vas deferens were investigated. 2 (+)‐Glaucine (2–18 μm) competitively inhibited contractions induced by noradrenaline and methoxamine with a pA2 value of about 6. 3 (+)‐Glaucine (2 and 18 μm) did not change the accumulation of tritium during incubation of the vas deferens with [3H]‐noradrenaline. 4 (+)‐Glaucine (0.3 nm‐‐0.1 mm) inhibited specific [3H]‐prazosin binding to membranes from rat vas deferens with a pKi value of 6.63, which is close to the pA2 value obtained against noradrenaline and methoxamine in functional studies. 5 In electrically‐stimulated rat vas deferens, (+)‐glaucine (0.3–10 μm) enhanced twitch contractions and competitively antagonized the inhibitory effect of clonidine with a pA2 value of 5.91. 6 In tissues incubated in depolarizing calcium‐free high‐potassium medium, (+)‐glaucine (30–80 μm) inhibited Ca2+‐induced contractions with depression of the maximal response at higher doses and with a pD'2 value of 3.65. Furthermore, (+)‐glaucine (50 μm) did not modify basal 45Ca uptake but strongly inhibited the influx of 45Ca induced by K+. 7 These results suggest that (+)‐glaucine has non‐selective α1‐ and α2‐adrenoceptor blocking properties. At higher doses, (+)‐glaucine shows calcium antagonist activity which may be responsible, at least in part, for the inhibition of the contractions induced by Ca2+ in calcium‐free high‐potassium medium.