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.
D000664:Amphibian Venoms / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D006146:Guanidines / Q000378:metabolism*; D006325:Heart Atria / Q000378:metabolism*; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013552:Swine
D000664:Amphibian Venoms; D006146:Guanidines; D011950:Receptors, Cholinergic; C038631:decahydrohistrionicotoxin