Phorbol Ester-Induced Periodic Contraction in Isolated Rabbit Jugular Vein

Phorbol Ester-Induced Periodic Contraction in Isolated Rabbit Jugular Vein

The present study was conducted to evaluate the effect of phorbol 12,13-dibutyrate (PDBu) on the contraction of rabbit jugular vein in vitro. PDBu concentrations of greater than 10 nM induced a periodic contraction which was composed of rapid contraction, plateau and slow relaxation. The frequency of periodic contraction increased as PDBu concentration increased. The PDBu-induced contraction was inhibited by staurosporine (100 nM), it was not changed by tetrodotoxin (1 μM). In Ca²⁺-free medium, PDBu induced a sustaining contraction, but not periodic contraction. Addition of Ca²⁺ to medium evoked periodic contraction which was inhibited by nifedipine, PDBu concentrations of greater than 0.1 μM increased ⁴⁵Ca²⁺ uptake without changing ⁴⁵Ca²⁺ efflux. Charybdotoxin and apamin, Ca²⁺-activated K⁺ channel blockers, did not affect the PDBu-induced periodic contraction, whereas tetraethylammonium (TEA) abolished the periodicity. Pinacidil (10 μM)., a potassium channel activator, blocked PDBu induced periodic contraction, which was recovered by glybenclamide (10 μM).. In high potassium solution, PDBu did not produce the periodic contraction. These results suggest that the PDBu-induced periodicity of contraction is modulated by voltage dependent Ca²⁺ channel and ATP-sensitive K⁺ channel.