Luminal ATP stimulates fluid and HCO3- secretion in guinea-pig pancreatic duct

1. The location of purinoceptors in the pancreatic duct and their role in r egulating ductal secretion have been investigated by applying ATP and UTP t o basolateral and luminal surfaces of pancreatic ducts isolated from the gu inea-pig pancreas. 2. Changes in intracellular Ca2+ concentration were measured by microfluoro metry in microperfused interlobular duct segments. Fluid and HCO3- secretio n were estimated by monitoring luminal pH and luminal volume in sealed duct segments microinjected with BCECF-dextran. 3. Both ATP and UTP (1 mu M) caused biphasic increases in intracellular Ca2 + concentration in pancreatic duct cells when applied to either the basolat eral or luminal membrane. 4. Luminal application of both ATP and UTP evoked fluid and HCO3- secretion . The maximum response to 1 mu M ATP or UTP was about 75% of that evoked by secretin. By contrast, basolateral application of ATP or UTP inhibited spo ntaneous secretion by 52% and 73 %, respectively, and secretin-evoked secre tion by 41 % and 38%, respectively. 5. The data suggest that luminal nucleotides may act in an autocrine or par acrine fashion to enhance ductal secretion while basolateral nucleotides, p erhaps released from nerve terminals, may have an inhibitory effect. The fa ct that both apical and basolateral Purinoceptors elevate intracellular Ca2 +, but that they have opposite effects on secretion, suggests that addition al signalling pathways are involved.