The effects of ammonia on pancreatic enzyme secretion in vivo and in vitro

Background: Recent studies clearly demonstrate that Helicobacter pylori (H. pylori) infection of the stomach causes persistent elevation of ammonia (N H3) in gastric juice leading to hypergastrinemia and enhanced pancreatic en zyme secretion. Methods: The aim of this study is to evaluate the influence of NH4OH on plasma gastrin level and exocrine pancreatic secretion in vivo in conscious dogs equipped with chronic pancreatic fistulas and on secreto ry activity of in vitro isolated acini obtained from the rat pancreas by co llagenase digestion. The effects of NH4OH on amylase release from pancreati c acini were compared with those produced by simple alkalization of these a cini with NaOH. Results: NH4OH given intraduodenally (i.d.) in increasing c oncentrations (0.5, 1.0, 2.0, 4.0, or 8.0 mM/L) resulted in an increase of pancreatic protein output, reaching respectively 9%, 10%, 19%, 16% and 17% of caerulein maximum in these animals and in a marked increase in plasma ga strin level. NH4OH (8.0 mM/L, i.d.) given during intravenous (i.v.) infusio n of secretin (50 pmol/kg-h) and cholecystokmin (50 pmol/kg-h) reduced the HCO3- and protein outputs by 35% and 37% respectively, as compared to contr ol obtained with infusion of secretin plus cholecystokinin alone. When panc reatic secretion was stimulated by ordinary feeding the same amount of NH4O H administered i.d. decreased the HCO3- and protein responses by 78% and 47 % respectively, and had no significant effect on postprandial plasma gastri n. In isolated pancreatic acini, increasing concentrations of NH4OH (10(-7) -10(-4) M) produced a concentration-dependent stimulation of amylase releas e, reaching about 43% of caerulein-induced maximum. When various concentrat ions of NH4OH were added to submaximal concentration of caerulein (10(-12) M) or urecholine (10(-5) M), the enzyme secretion was reduced at a dose 10( -5) M of NH4OH by 38% or 40%, respectively. Simple alkalization with NaOH o f the incubation medium up to pH 8.5 markedly stimulated basal amylase secr etion from isolated pancreatic acini, whereas the secretory response of the se acini to pancreatic secretagogues was significantly diminished by about 30%. LDH release into the incubation medium was not significantly changed i n all tests indicating that NH4OH did not produce any apparent damage of pa ncreatic acini and this was confirmed by histological examination of these acini. Conclusions: 1. NH4OH affects basal and stimulated pancreatic secret ion. 2. The excessive release of gastrin may be responsible for the stimula tion of basal pancreatic enzyme secretion in conscious animals, and 3. The inhibitory effects of NH4OH on stimulated secretion might be mediated, at l east in part, by its direct action on the isolated pancreatic acini possibl y due to the alkalization of these acini.