Electrophysiological studies of chemoreceptors sensitive to pyridine on the crayfish walking leg. II. Characteristics of inhibitory molecules

The effect of substituted pyridines on the response of singlepyridine-sensitive cells from crayfish walking legs was investigatedelectrophysiologically. Seven p-substituted pyridines, actingreversibly, were identified as specific antagonists at the pyridinereceptor. The maximum saturation frequency of the response toagonists was reached in the presence of antagonists but thedose–response curves of the agonists were shifted in parallelto the right along the concentration axis. Schild plots of threehighly effective antagonists with six agonists were linear witha slope close to one, indicating competitive antagonism. Theinhibition constants yielded a K₁ value of {small tilde}4–8µmol for the most effective antagonist, 4-(4-nitrobenzyl)pyridine,which had only one order of magnitude lower affinity than themost effective agonist 2,3'-bipyridyl. The antagonists 2,4'-bipyridyland 4-benzylpyridine had K¹ values of 6–10 µmol,followed by 4-acetylpyridine with a K¹ value of 30–70µmol. The rank order of inhibitory potency of the differentantagonists was found to be the same for all units tested. Comparingelectronic effects (Hammett values and pKa values) of the substitutentsin p- and m-position showed that inhibitory effectiveness decreasedwith a decrease in pKa and an increase in Partition coefficientswere determined for 10 agonists and the antagonists which weregenerally more lipophilic than the agonists. A hypotheticalreceptor site is proposed.