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.