Contractile and relaxant effects of tetrapentylammonium ions in rat isolated mesenteric artery

Both contractile and relaxant responses to tetrapentylammonium ions (TPA⁺) were studied in rat isolated mesenteric artery. TPA⁺ (5-10 μmol/l) caused a sustained increase of muscle tension. The contractile effect of TPA⁺ (10 μmol/l) was dependent upon the presence of extracellular Ca²⁺ but independent of the presence of endothelium. TPA⁺ (10-50 μmol/l) induced biphasic contraction, and the amplitude of peak and sustained tension decreased with increasing TPA⁺ concentration. TPA⁺ (100-300 μmol/l) only produced monophasic contraction. TPA⁺ (50 μmol/l) abolished the transient contraction induced by caffeine (10 mmol/l) or phenylephrine (1 μmol/l) in the absence of extracellular Ca²⁺. Nifedipine and verapamil concentration-dependently reduced the TPA⁺-induced contraction with respective IC₅₀ values of 1.34 ± 0.24 and 9.46 ± 1.36 nmol/l, these values were similar to 1.35 ± 0.21 and 16.07 ± 1.71 nmol/l, respectively, for the inhibitory effects of nifedipine and verapamil on the high K⁺ (60 mmol/l)-induced contraction. TPA⁺ (> 10 μmol/l) concentration-dependently reduced the phenylephrine (± μmol/l)-, U46619 (30 nmol/l)-, endothelin I (10 nmol/l)- and high K⁺ (60 mmol/l)-induced sustained tension with respective IC₅₀ values of 53.7 ± 9.5, 31.9 ± 5.3, 30.9 ± 3.4 and 20.9 ± 2.8 μmol/l. The present results indicate that TPA⁺ at low concentrations could contract the arterial smooth muscle probably through promoting Ca²⁺ influx. At higher concentrations (> 20 μmol/l), TPA⁺ relaxes arterial smooth muscle probably through inhibition of both nifedipine-sensitive Ca⁺ channels and internal Ca²⁺ release. TPA⁺, unlike other quaternary ammonium ions, could therefore act at multiple sites in arterial smooth muscle.