The effects of pH on the affinity of pirenzepine for muscarinic receptors in the guinea-pig ileum and rat fundus strip.
1 Dose-ratios obtained with pirenzepine on the guinea-pig ileum at 30 degrees C are indistinguishable from those obtained at 37 degrees C. 2. In 0.1 M NaCl at 37 degrees C the pKa of pirenzepine for the loss of its last ionizable proton is 8.2. The ionization of pirenzepine is therefore markedly affected by changes in pH in the physiological range. 3 In experiments with pirenzepine on guinea-pig ileum and rat fundus made over a range of pH, the dose-ratio increases with the proportion of the protonated form present. As expected, the slope of the graph of dose-ratio against proportion protonated depends on the concentration of antagonist. The changes in pH produce only small effects on dose-ratios obtained with pirenzepine monomethiodide. These effects of pH can account for some of the differences between estimates of the affinity of pirenzepine. 4 The logarithm of the affinity constant of the protonated form of pirenzepine for the receptors in guinea-pig ileum is estimated to be 6.93, compared with 6.94 for the receptors in rat fundus. However, for the non-protonated form the values appear to be below 5 for the ileum compared with about 6.4 for the rat fundus.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D001570:Benzodiazepinones / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005748:Gastric Fundus / Q000378:metabolism; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D010890:Pirenzepine; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D001570:Benzodiazepinones; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D010890:Pirenzepine