Excitatory and inhibitory actions of vasopressin on colonic excitation-contraction coupling in dogs.

BACKGROUND & AIMS Vasopressin, a circulating hormone and agent used to treat gastrointestinal bleeding, affects gastrointestinal motility. Both excitatory and inhibitory responses that may be caused by species differences or concentration-dependent effects of this hormone have been reported. This study examined the actions of vasopressin on the canine colon and studied the mechanism underlying the excitatory effects of vasopressin. METHODS Intracellular microelectrodes and isometric force measurements were used to measure vasopressin responses in muscle strips. The patch-clamp technique was used to record arginine vasopressin activation of nonselective cation currents in isolated myocytes. RESULTS Vasopressin (10(-12) to 10(-9) mol/L) increased electrical slow waves and enhanced phasic contractions. Atropine and tetrodotoxin did not alter the responses to vasopressin. In myocytes, vasopressin activated a nonselective cation conductance at concentrations that enhanced slow waves. Vasopressin (> 5 x 10(-8) mol/L) caused a tetrodotoxin- or NG-nitro-L-arginine methyl ester-insensitive inhibition of slow waves and contractile activity. A V1-receptor antagonist shifted the effects of vasopressin to higher concentrations. Immunohistochemistry showed expression of vasopressin-like immunoreactivity within the colonic wall, suggesting that local concentrations may exceed circulating levels. CONCLUSIONS These data document the concentration dependence of the biphasic effects of vasopressin and provide a mechanism for the excitatory effects of vasopressin at physiological levels.