The effect of pH changes and ionization on the action of epinephrine upon the isolated rabbit ileum

Abstract

This study demonstrates that the activity of epinephrine on the isolated rabbit ileum is related to the quantity of epinephrine present as the cation in the tissue bath at a given pH. Isolated segments of rabbit ileum were exposed to doses of epinephrine in Tyrode solution which varied in pH from 6.4 to 8.8. The change of pH did not significantly alter the spontaneous contractile activity of an intestinal segment; however, epinephrine-induced inhibition of intestinal activity varied with changes of pH. At oH 6.4-7.8 the catecholamines exist predominantly as cations. The relative amount of the cationic form of these compounds does not appreciably change unless the pH of a solution of catecholamine is raised above 7.8. The alteration of pH from 7.8 to 8.8 was great enough to vary the fraction of epinephrine present as a cation from 90 to 52% of a given total dose of drug. As the pH was raised above 7.8, epinephrine activity decreased in proportion to the decreased concentration of epinephrine cation.