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Brt/wstlrr, Mtiryliind 20014, U.S.A .Abstract: The effects of hyperbaric pressure in helium-oxygen atmospheres on a proteoglycolipid, isolated from rat gastrocnemius tissue, with binding specificity for cholinergic ligands have been studied at six pressure levels in the ranges of 14.7 to 400 psi (1-27 atm). The binding of acetylcholine, abungarotoxin, tubocurarine, decamethonium, and nicotine t o the proteoglycolipid decreased with increasing pressure, the greatest binding losses occurring in the 14.7-100 psi range. The loss of [l'C]acetylcholine and 1251-labeled a-bungarotoxin binding to the proteoglycolipid with increasing pressure was augmented in the presence of cholinergic antagonists such as nonradioactive a-bungarotoxin, tubocurarine, and decamethonium. T h e presence of hexamethonium, a ganglionic cholinergic antagonist, in the reaction mixtures appeared to prevent loss of acetylcholine and a-bungarotoxin binding with increasing pressure. Saturation of the proteoglycolipid with acetylcholine at each pressure level indicated that the conformation of the isolated macromolecule may be distorted with increasing pressure, resulting in alterations to specific ligand-binding sites. The significance of these results is discussed in relation to the effects of pressure on in ,.ir*o neural processes.