Relaxation of Evoked Contractile Activity of Isolated Guinea-Pig Ileum by (±)-Kavain

Abstract

Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (±)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (±)-Kavain (1 µM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 µM), by BAY K 8644 (0.3 µM), or by substance P (0.05 µM). (±)-Kavain also inhibited the contractile responses induced by raising the extracellular K⁺ concentration from 4 to 20 mM and by blocking the K⁺ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After preincubation with 1 µM nifedipine, carbachol (1 µM) evoked 18.2 ± 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (±)-kavain (400 µM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 µM) evoked 27.0 ± 6.2% of the control response in untreated ileum. These contractions were also blocked by (±)-kavain (400 µM). However, (±)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or β-escin. Moreover, it failed to affect Ca²⁺-evoked contractions of skinned muscles. These results suggest that the kava pyrone (±)-kavian may act in a nonspecific musculotropic way on the smooth muscle membrane.

(±)-Kavain - Piper methysticum - Piperaceae - guinea-pig ileum - contraction - relaxation