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Molecular Pharmacology

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Abstract

Evidence of paired M2 muscarinic receptors.

L T Potter, L A Ballesteros, L H Bichajian, C A Ferrendelli, A Fisher, H E Hanchett and R Zhang
Molecular Pharmacology February 1991, 39 (2) 211-221;
L T Potter
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L A Ballesteros
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L H Bichajian
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C A Ferrendelli
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A Fisher
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H E Hanchett
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R Zhang
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Abstract

Binding assays involving various antagonists, including N-[3H] methylscopolamine, [3H]quinuclidinyl benzilate, AFDX-116, pirenzepine, and propylbenzilylcholine mustard, disclosed only a single population of M2 muscarinic receptors in membranes from the rat "brainstem" (medulla, pons, and colliculi). However, competition curves between N-[3H]methylscopolamine and various agonists, including oxotremorine, cis-dioxolane, and acetylethylcholine mustard, showed approximately equal numbers of guanine nucleotide-sensitive high affinity (H) sites and guanine nucleotide-insensitive low affinity (L) sites. This 50% H phenomenon persisted in different buffers, at different temperatures, after the number of receptors was halved (and, thus, the remaining receptor to guanine nucleotide-binding protein ratio was doubled), after membrane solubilization with digitonin, and when rabbit cardiac membranes were used instead of rat brainstem membranes. Preferential occupation of H sites with acetylethylcholine mustard, and of L sites with quinuclidinyl benzilate or either mustard, yielded residual free receptor populations showing predominantly L and H sites, respectively. Low concentrations of [3H]-oxotremorine-M labeled only H sites, and the Bmax for these sites was 49% of the Bmax found with [3H]quinuclidinyl benzilate plus guanine nucleotide. These and other results are most consistent with the idea that H and L receptor sites exist on separate but dimeric receptor molecules and with the hypothesis that only the H receptors cycle between high and low affinity, depending upon interactions between this receptor molecule and a guanine nucleotide-binding protein.

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Molecular Pharmacology
Vol. 39, Issue 2
1 Feb 1991
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Abstract

Evidence of paired M2 muscarinic receptors.

L T Potter, L A Ballesteros, L H Bichajian, C A Ferrendelli, A Fisher, H E Hanchett and R Zhang
Molecular Pharmacology February 1, 1991, 39 (2) 211-221;

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Abstract

Evidence of paired M2 muscarinic receptors.

L T Potter, L A Ballesteros, L H Bichajian, C A Ferrendelli, A Fisher, H E Hanchett and R Zhang
Molecular Pharmacology February 1, 1991, 39 (2) 211-221;
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