Acidification in the Rat Proximal Jejunum

Abstract

Acidification of solutions by rat proximal jejunum was investigated in everted sacs, segments and in perfused in vivo loops. Acidification which declines down the jejunum, increased with increasing mucosal glucose concentration, reaching a maximal value. Derived Michaelis-Menten data gave an apparent Km of 0.05mM and a Vmax of 1.01 (ugH+/mg/hr). Acidification was uninhibited by 10mM mucosal L-β-phenylalanine and unstimulated by mucosal 10mM pyridoxal phosphate: it was stimulated by glucose-1- and -6-phosphate. Acidification was unaffected by 10mM mucosal acetazolamide and 10mM ouabain which excluded bicarbonate movement and made active sodium transfer unlikely, as causing acidification. Acidification was diminished by anoxia, by phlorrhizin and by DNP at concentrations that prevent oxidative processes, indicating the metabolic dependency and excluding anoxia as a source of acidification. Unaffected by histamine (10mM) and EDTA (10mM) , acidification is distinct physiologically, from gastric acid production. The ineffectiveness of acetazolamide and the inability of mucosal lactic acid, pyruvic acid production and amino acid loss to fully account for acidification in sacs, segments and loops, makes less likely the existing theory of acidification being caused by bicarbonate movement and lactic acid production. The non-metabolisable sugars 3-O-methylglucose and galactose do not stimulate, the metabolisable sugars glucose, mannose and fructose stimulate acidification, indicating the metabolic nature of the origin of the protons. Similarly, mucosal ATP (10mM) which does not enter the tissues causes an increase in acidification, not due to the chelating ability of ATP. Acidification is most markedly inhibited by aminophylline (10mM) implicating the importance of ATP turnover via the adenyl cyclasephosphodiesterase system. Imidazol (10mM) has no effect. It is proposed that acidification is not a passive process but the result of external hydrolysis of ATP at the surface of epithelial cells. This concept is examined in relation to the microclimate hypothesis and the implications of acidification in the transfer of weakly-ionising substances discussed.