Interplay between nitric oxide and VIP in CCK-8-induced phasic contractile activity in the rabbit sphincter of Oddi.

AIM The sphincter of Oddi (SO) plays an important role in delivery of bile into the duodenum. To establish whether vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) were involved in phasic contractile activity of the rabbit SO stimulated by cholecystokinin-octapeptide (CCK-8). METHODS Isolated SO muscle rings were cleaned of fat and mounted horizontally on two small L-shaped hooks one of which was connected to a force transducer for the measurement of isometric tension. The experiments were carried out in a thermostatically controlled (37+/-0.2 degrees) organ bath (5 mL) containing Krebs solution. The organ fluid was gassed with 95% O(2) and 50 mL/L CO(2) to keep the pH at 7.40+/-0.05. Contractile responses to CCK-8 (1 micromol/L) were evaluated in the presence and absence of N(G)-nitro-L-arginine (LNNA), an inhibitor of NO synthase (100 micromol/L), and (p-chloro-D-Phe(6)-Leu(17))-VIP (VIPa, 30 micromol/L), a VIP receptor antagonist. RESULTS CCK-8 stimulated the phasic activity of the SO. NO synthase inhibition increased the frequency and amplitude of contractions with a slight increase in developed tension. Pre-incubation with VIPa also attenuated this CCK-8 effect. The combined application of LNNA and VIPa abolished the phasic activity of the muscle rings with a marked increase in tension in response to CCK-8. CONCLUSION VIP and NO together contribute to an increase in phasic activity of SO.