Inhibitory Effect of Ouabain and Acetazolamide on Secretin‐stimulated Pancreatic Exocrine Secretion in Anaesthetized Dog

Abstract

1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were added together, the inhibitory effects were significantly higher than for each drug alone. 3. The bicarbonate concentration in the pancreatic juice was decreased and the chloride concentration was increased by ouabain and acetazolamide, but sodium and protein concentrations were not modified. 4. The results suggest that the Na+,K+-ATPase and carbonic anhydrase activities play important roles in water and electrolyte secretion, and that ouabain and acetazolamide inhibit secretin-stimulated pancreatic secretion by acting on different systems in the exocrine cells in dogs.

Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of Na+,K+-ATPase in pancreatic acinar cells

“…Effects of PF-3758309 and LCH-7749944, PAK4 inhibitors, on Na ϩ ,K ϩ -ATPase activity. One of the main physiological functions of secretin and VIP in the pancreas is to stimulate pancreatic fluid secretion, which is dependent on activation of Na ϩ ,K ϩ -ATPase (9,32,34,49,64). To investigate the possible effect of PAK4 directly on Na ϩ ,K ϩ -ATPase activation, we assessed hormonal activation of Na ϩ ,K ϩ -ATPase activation by incubating pancreatic acini with the PAK4 inhibitors, PF-3758309 (0.1 nM) and LCH-7749944 (30 M), and with ouabain (Na ϩ ,K ϩ pump inhibitor as control, 1 mM) for 3 h and then stimulated with VIP (10 nM) or secretin (10 nM) for 15 min.…”

Alteraciones en células secretoras del páncreas exocrino en modelos experimentales de fibrosis quística y pancreatitis aguda

“…45,240,300 El bloqueo de la Na + ,K + -ATPasa por ouabaína provoca una inhibición de la secreción de HCO 3 − en diferentes especies. 43,158,162,195,336 También en la línea celular CAPAN-1 la ouabaína bloquea la corriente transepitelial estimulada por la forskolina, inhibiendo la secreción de HCO 3 − . 273 Todos estos resultados indican que la Na + ,K + -ATPasa, o más concretamente el gradiente de Na + creado por ella a través de la membrana basolateral, juega un papel fundamental en la secreción pancreática ductular.…”