EFFECT OF DIMETHADIONE ADMINISTERED INTRAVENOUSLY ON PANCREATIC-SECRETION IN DOGS

In order to detect both pancreatic excretion of dimethadione (DMO), a weak organic acid, and the effect of pancreatic DMO on secretin-stimul ated pancreatic secretion, DMO was given intravenously to dogs with pa ncreatic fistulae at a dose of 50, 100 and 200 mg/kg. DMO was promptly excreted into pancreatic juice; the concentration decreased exponenti ally as it did in plasma at the highest dose of the compound. Ar equil ibrium of DMO between pancreatic juice and plasma, the DMO concentrati on in the juice depended directly on that in plasma; the juice/plasma concentration ratios for DMO exceeded 1.0, ranging from 1.7 to 2.1. Pa ncreatic DMO caused a small but significant decrease in the water, bic arbonate and sodium secretion at non-equilibrium, and in the bicarbona te secretion at equilibrium. A decrease in the bicarbonate secretion m ay result largely from the buffer action of bicarbonate on protons pro vided by the undissociated form of DMO. The sum of both bicarbonate an d chloride concentrations in pancreatic juice decreased with the incre ased DMO concentration in the juice, implying that DMO may compete wit h the secretion of bicarbonate and/or chloride across the apical membr ane of the duct cell. Pancreatic DMO can act as a non-specific inhibit or of pancreatic water and electrolyte secretions.