Ultraviolet light-induced labeling by noncompetitive blockers of the acetylcholine receptor from Torpedo marmorata.

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Abstract
Reversible ligands were attached covalently to membrane-bound acetylcholine receptor from T. marmorata electric organ by a method which is generally applicable and does not require the synthesis of specially designed molecules. UV irradiation of the receptor in the presence of [3H]trimethisoquin, [3H]phencyclidine, or [3H]perhydrohistrionicotoxin resulted in the labeling of the binding site(s) for these noncompetitive blockers of the permeability response. The labeling of the .delta. chain was enhanced by carbamoylcholine, and this increase was blocked by snake .alpha.-toxins. The effect of carbamoylcholine [3H]trimethisoquin binding was more pronounced than with the other abolished by unlabeled histrionicotoxin. These 3 compounds interact with the high-affinity site for noncompetitive blockers. Incorporation of radioactivity also occurred into the .alpha. chain, but either was insensitive to cholinergic effectors or decreased in the presence of carbamoylcholine (or snake .alpha.-toxin), probably as a result of an interaction with the acetylcholine-binding site. In contrast to the other noncompetitive blockers tested, [3H]chlorpromazine heavily labeled the 4 receptor polypeptides (.alpha., .beta., .gamma. and .delta.), and this labeling was enhanced by carbamoylcholine and decreased by histrionicotoxin. The data indicate a contribution of the .delta. chain to the binding site(s) of several well-characterized noncompetitive blockers and suggest that other receptor polypeptides may also contribute to this binding.