Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens.

Context: Butylidenephthalide (Bdph) has been reported to inhibit rat uterine contractions, but significantly potentiate the noradrenaline (NA)-induced contractions in guinea-pig vas deferens (GPVDs). Objective: The present study elucidates the binding specificity of Bdph in GPVD to potentiate contractions. Materials and methods: Electrical field stimulation (EFS, supramaximal voltage, 1 ms and 1 Hz) or exogenous NA (50 mu M) was applied to the GPVD in Krebs or 1/10 Mg-Tyrode's solution, respectively. After the clonidine (10 nM)-induced twitch inhibition or the exogenous NA-induced contractions reached a constant, Bdph (50 mu M) was added 2 min prior to the subsequent addition of NA (50 mu M). Three experiments were performed. In the presence of Bdph (100 mu M), the release of NA in the medium and remaining NA content in the tissues were determined after EFS-stimulation. Results: Bdph (100 mu M) significantly antagonized the clonidine (10 nM)-induced twitch inhibition from 22.5 +/- 2.1 to -11.4 +/- 1.6% (n = 6) and dibutyryl-cAMP (300 mu M) from 25.7 +/- 3.2 to 7.9 +/- 4.0% (n = 8). Bdph (100 mu M) significantly increased the electrically stimulated release of NA from 393.0 +/- 109.5 to 1000.0 +/- 219.1 ng/g (n = 6). Bdph (50 mu M) potentiated the exogenous NA (50 mu M)-induced contractions from 3.0 +/- 0.06 to 3.9 +/- 0.06 g (n = 3), but after washout of Bdph, the response to NA gradually curtailed. Discussion and conclusions: Bdph action may be through the nonspecific binding of the butylidene group to prejunctional alpha(2)- and postjunctional alpha(1)-adrenoceptors to reversibly block K+ channels, and irreversibly block VDCCs on the smooth muscle cell membrane, respectively.