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

Abstract

Lapachol, α and β-lapachone are naphthoquinones extracted from species of Tabebuia that have shown antiinflammatory, 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, α and β-lapachone inhibited the phasic contractions induced by both carbachol (IC50 = 1.5 ± 0.2 × 10-4; 7.3 ± 0.9 × 10-5 and 3.2 ± 0.5 × 10-5 M, respectively) and histamine (IC 50 = 3.6± 0.5; 3.6 ± 0.7 and 3.3 ± 0.6 × 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 × 10-5 M, respectively); carbachol (EC50 = 2.6 ± 0.7; 3.5 ± 0.5 and 2.2 ± 0.7 × 10-5 M, respectively) or histamine (EC50 = 3.0 ± 0.8; 1.1 ± 0.3 and 3.3 ± 0.6 × 10-5 M, respectively) in a concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-gated calcium channels (Ca v). β-lapachone antagonized (pD'2 = 5.73 ± 0.12; slope = 1.51 ± 0.05) CaCl2-induced contractions in depolarizing medium nominally without Ca2+. The finding that β-lapachone inhibited the tonic contractions induced by S-(-)-Bay K8644 (EC50 = 1.4 ± 0.1 × 10-5 M) is suggestive that the L-type CaV is involved. In conclusion, lapachol, α and β-lapachone showed non-selective spasmolytic activity in guinea-pig ileum, and β-lapachone exerts this effect by to blockade of L-type CaV channels.