Histrionicotoxin and alkylguanidine interactions with the solubilized and membrane-bound muscarinic acetylcholine receptor from porcine atria.

The interaction of alkylguanidines and decahydrohistrionicotoxin with the membrane-bound and solubilized muscarinic acetylcholine receptor (mAcChR) from porcine atria was described. Alkylguanidines with alkyl chain lengths from one to ten carbons displaced L-[3H]quinuclidinyl benzilate (L-[3H]QNB) competitively from a single class of sites for the membrane-bound mAcChR. From a plot of -1n Ki versus alkyl carbon chain number, a value of -(473 +/- 30) cal/mol was estimated as the energetic contribution per methylene group to the total binding energy. The binding of alkylguanidines to the digitonin/cholate solubilized mAcChR was complex in nature resulting in titration curves that did not obey the law of mass action for simple competitive inhibition at higher alkyl carbon numbers and a sigmoidal plot of -1n Ki versus carbon number. Decahydrohistrionicotoxin bound in a competitive manner versus L-[3H]QNB to both the membrane-bound (Ki = (6.9 +/- 1.4) X 10(-6) M) and the solubilized (Ki = (1.5 +/- 0.3) X 10(-5) M) preparations.