Pharmacological Evaluation of the Ca-Channels Role in the Inhibitory Effects of Thymoquinone on the Contractile Responses of Rat Isolated Vas Deferens

It has been recently shown that thymoquinone (TQ), the major constituent of Nigella sativa seeds, has inhibitory effects on contractile responses of guinea-pig trachea and ileum, probably through a non-selective antagonistic activity on serotonergic and histaminergic receptors. The aim this study was to evalute the effects of TQ on contractile responses of rat vas deferens using tension-recording technique. Male rats (6 groups of 4 each) were stunned by a blow to the head and exsanguinated. The vas deferens were dissected out and placed in Krebs solution in an organ bath set up (under an initial load of 0.5 g tension. The effects of TQ (10, 20, 40, 80, 100 M) on contractile responses of vas deferens to norepinephrine (NE) (10 M), dopamine (DA) (10 M) potassium chloride (KCl) (80 mM), and repetitive electrical field stimulation (REFS) (frequency = 20 Hz, duration = 0.1 ms, intensity=130 V) were recorded by an isometric transducer. The amplitude of REFS-evoked contractile responses, were also recorded in Ca2+-free medium and in the presence of cumulative concentrations of CaCl2 (0.1, 0.2, 0.4, 1, 2 mM). The results showed that TQ at concentrations less than 100 M decreased the amplitude of contractile responses of vas deferens induced by NE, DA, KCl, and REFS. The minimum effective concentration of TQ was 40 M for NE- and DA-, and 20 M for KCl- and REFS-induced contractions (p<0.01 and p<0.001, respectively). Addition of cumulative concentrations of CaCl2 in the presence of TQ (80 M) failed to increase the amplitude of contractions induced by REFS, which were suppressed in Ca2+-free medium (p<0.001). These results indicate that thymoquinone has inhibitory effects on the contractile responses of rat isolated vas deferens and exerts its effects at least in part through the blockade of calcium channels in vas deferens smooth muscle cells.