Spasmolytic activity of lapachol and its derivatives, α and β-lapachone, on the guinea-pig ileum involves blockade of voltage-gated calcium

Lapachol, a and P-lapachone are naphthoquinones extracted from species of. Tabeuia that have-shown anti inflammatory, antibacterial, anticancer and trypanosomicidal. properties. The aim of this work was to investigate the spasmolytic effect of these naphthoquinones on the guinea-pig ileum, since other naphthoquinones are known to depress the contractile activity of smooth muscles. Lapachol, a and P-lapachone inhibited the phasic contractions induced by both carbachol (IC50 = 1.5 +/- 0.2 x 10(-4); 7.3 +/- 0.9 x 10(-5) and 3.2 +/- 0.5 x 10(-5) M, respectively) and histamine (IC50 = 3.6 +/- 0.5; 3.6 +/- 0.7 and 3.3 +/- 0.6 x 10(-5). M, respectively). These compounds also relaxed the ileum pre-contracted with KCl (EC50 = 1.2 +/- 0.4; 4.3 +/- 0.8 and 2.7 +/- 0.2 x 10(-5) M, respectively); carbachol (EC50 = 2.6 +/- 0.7; 3.5 +/- 0.5 and 2.2 +/- 0.7 x 10(-5) M, respectively) or histamine (EC50 = 3.0 +/- 0.8; 1.1 +/- 0.3 and 3.3 +/- 0.6 x 10(-5) M, respectively) in a concentration dependent manner. This effect is probably due to inhibition of calcium influx through voltagegated calcium channels (Ca-v). beta-lapachone antagonized (pD'(2) = 5.73 +/- 0.12; slope = 1.51 +/- 0.05) CaCl2-induce contractions in depolarizing medium nominally without Ca2+. The finding that beta-lapachone, inhibited the tonic contractions induced by S-(-)-Bay K8644 (EC50 = 1.4 +/- 0.1 x 10(-5) M) is suggestive that the L-type Ca-v is involved. In conclusion, lapachol, alpha and beta-lapachone showed non-selective spasmolytic activity in guinea-pig ileum, and beta-lapachone exerts this effect by to blockade of L-type Cav channels.