Selective enhancement of antagonist ligand binding at muscarinic M2 receptors by heparin due to receptor uncoupling

doi:10.1016/0014-2999(95)00674-5

European Journal of Pharmacology

Volume 296, Issue 1, 18 January 1996, Pages 113-118

https://doi.org/10.1016/0014-2999(95)00674-5 Get rights and content

Abstract

The selectivity of heparin in inducing potentiation of binding of antagonist ligands to muscarinic receptors was investigated at the five known subtypes of muscarinic receptors. The effects of heparin on binding of [³H]N-methylscopolamine at equilibrium was studied in Chinese hamster ovary (CHO) cells which express each of the individual muscarinic receptor subtypes and in membranes prepared from these cells. Heparin markedly increased equilibrium binding of subsaturating concentrations of the ligand only in membranes of CHO cells which express muscarinic M₂ receptors. These effects of heparin were qualitatively similar to those obtained in heart membranes. In contrast, heparin did not influence ligand binding to muscarinic M₂ receptors in intact cells. The positive cooperative effects of heparin at muscarinic receptors were abolished following treatment of cells with pertussis toxin. The latter treatment by itself resulted in a significant increase in [³H]N-methylscopolamine binding. Taken together with previous reports of heparin-induced uncoupling of receptors and G-proteins, these data suggest that the effects of heparin on ligand binding to muscarinic M₂ receptors might be due to disruption of receptor-G-protein interactions which results in enhancement of binding of antagonist ligands to the receptor.

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Selective enhancement of antagonist ligand binding at muscarinic M2 receptors by heparin due to receptor uncoupling

Abstract

Biochem. Pharmacol.

Eur. J. Pharmacol.

Biochem. Pharmacol.

Differential effects of suramin on the coupling of receptors to individual species of pertussis toxin sensitive guanine nucleotide binding proteins

Biochem. J.

Negative and positive inotropic responses to muscarinic agonists in guinea pig and rat atria in vitro

J. Pharmacol. Exp. Ther.

Estimation of the affinities of allosteric ligands using radioligand binding and pharmacological null methods

Mol. Pharmacol.

Heparin, dextran and trypan blue allosterically modulate M2 muscarinic receptor binding properties and interfere with receptor-mediated inhibition of adenylate cyclase

J. Pharmacol. Exp. Ther.

Role of intercellular and intra-cellular communication by nitric oxide in coupling of muscarinic receptors to activation of guanylate cyclase in neuronal cells

J. Neurochem.

Complex allosteric modulation of cardiac muscarinic receptors by protamine: potential model for putative endogenous ligands

Mol. Pharmacol.

Identification of allosteric antagonists of receptor-guanine nucleotide-binding protein interactions

Mol. Pharmacol.

Selective enhancement of antagonist ligand binding at muscarinic M₂ receptors by heparin due to receptor uncoupling

Heparin, dextran and trypan blue allosterically modulate M₂ muscarinic receptor binding properties and interfere with receptor-mediated inhibition of adenylate cyclase