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Effect of pH on Muscarinic Acetylcholine Receptors from Rat Brainstem
Author(s) -
Anthony Betty L.,
Aronstam Robert S.
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb13003.x
Subject(s) - muscarinic acetylcholine receptor , acetylcholine , neuroscience , brainstem , muscarinic acetylcholine receptor m4 , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m3 , acetylcholine receptor , muscarinic acetylcholine receptor m1 , chemistry , receptor , muscarinic acetylcholine receptor m5 , endocrinology , biology , biochemistry
The effect of hydrogen ion concentration on ligand binding to muscarinic acetylcholine receptors was studied in membranes isolated from rat brainstem. The binding of [ 3 H]methylscopolamine was constant between pH 7 and 10. The affinity, but not the number, of [ 3 H]‐methylscopolamine binding sites decreased below pH 7; at pH 4 little binding was detected. When brainstem membranes were incubated at various pH levels from 3 to 11 for 1 h and then returned to pH 8, [ 3 H]methylscopolamine binding affinity was restored to control levels. Carbamylcholine binding affinity was also depressed in media of low pH. However, this decrease was permanent after a 1‐h incubation at pH 4 (i.e. carbamylcholine affinity was not restored on raising the pH to 8). The capacity of a guanine nucleotide to affect carbamylcholine was also abolished by a 1‐h incubation at pH 4, and was not restored by raising the pH. The guanine nucleotide‐dependent regulatory protein may be irreversibly inactivated or dissociated from the receptor at low pH. The receptor's binding subunit, on the other hand, appears to be much less sensitive to hydrogen ion concentration.