AN EFFECT OF pH UPON EPINEPHRINE INOTROPIC RECEPTORS IN THE TURTLE HEART

¹ Departments of Pharmacology, Marquette University, Milwaukee, Wisconsin, and University of Michigan, Ann Arbor, Michigan

The effect of pH upon the rate of deterioration of the biological activity of epinephrine has been determined in the isolated turtle heart preparation. In no case was there a significant (P < .01) decrease in biological activity of epinephrine solutions at pH 7.5, 8.5 or 9.5 within 45 minutes after preparation.

The greatest degree of positive inotropic activity obtained with epinephrine (5 x 10^-8 M) in the turtle heart during summer months over the pH range of 6.5 to 9.5 was observed to occur at pH 7.5. This pattern was observed when successive doses of epinephrine were given to the same turtle hearts at pH 6.5, 7.5, 8.5 and 9.5 or to four different groups of hearts in which the epinephrine response was elicited at one pH value in each group.

The dose-response relationship of epinephrine cation to positive inotropic activity obtained at a given pH value strongly implicates the cation as the active form of the drug.

Our data also indicate that the dose-response relationship of epinephrine cation to positive inotropic activity is quantitatively moderated by the pH of the perfusion medium. This observation has led us to propose the hypothesis that pH may exercise a direct effect upon the epinephrine inotropic receptor mechanism, altering its quantitative relationships with the drug molecule.