Effects of pH on in vitro gallbladder responses to cholecystokinin octapeptide.

We investigated the effect of pH change on octapeptide cholecystokinin's ability to contract guinea pig gallbladder strips. In the absence of exogenous drugs, pH changes had no demonstrable effect on gallbladder tension. However, when gallbladder strips were contracted with CCK-OP at pH 7.3, increasing the pH in the muscle bath to 7.8 produced further increases in tension at each dose studied (P less than 0.025). Subsequently, decreasing the bath pH to 6.9 decreased the strip tension to less than that observed at pH 7.3 (P less than 0.025). Reversing the order in which these pH alterations were made produced similar results; a pH decrease from 7.3 to 6.9 decreased the response to CCK-OP at the two highest doses (P less than 0.025), while subsequent elevation of pH raised the tension to levels greater than those observed at pH 7.3 (P less than 0.01). Furthermore, contracting the strips at pH 8.0 and slowly decreasing pH at a rate of 0.1 pH units per minute consistently produced an acceleration of tension decay as pH fell. After contracting the strip at pH 6.7, slow increases in pH reversed the tension decay and enhanced the contractile response as pH was increased from 6.7 to 8.0. These results demonstrate that pH changes alter the gallbladder contractile response to cholecystokinin. Although this phenomenon has been reported for a number of other physiologic agents, we believe this is the first such demonstration for a peptide hormone.

pH-dependent activity of H1- and H2-histamine receptors in guinea-pig gallbladder.

Utilizing histamine and selective agonists for H1- and H2-receptors, we examined the pH dependence of histamine-stimulated tension changes in guinea-pig gallbladder, which contains both contracting H1-receptors and relaxing H2-receptors. In muscle strips contracted with histamine and pH 7.3, increasing pH to 7.8 raised tension further (P less than .025), while decreasing pH caused a fall in tension (P less than .025). The H2-agonist Dimaprit relaxed tension at pH 7.3 and increasing the pH decreased the relaxation (p less than .0125). Contractions in response to H1-agonist 2-pyridylethylamine at pH 7.3 were unchanged when pH was elevated but decreased when pH was lowered (P less than .05). Tension changes in response to slow pH alterations suggested that H1-receptor activity is inhibited below pH 7.1 and H2-receptor activity is inhibited above pH 7.6. These reversible changes in activity probably reflect changes at H1- and H2-receptors rather than alterations in the ionic species of histamine.