Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor

David Jacoby, Gerald J. Gleich, Allison Fryer

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

The effect of human eosinophil major basic protein (MBP), as well as other eosinophil proteins, on binding of [3H]N-methylscopolamine ([3H]NMS; 1 × 10-10 M) to muscarinic M2 receptors in heart membranes and M3 receptors in submandibular gland membranes was studied. MBP inhibited specific binding of [3H]NMS to M2 receptors but not to M3 receptors. MBP also inhibited atropine-induced dissociation of [3H]-NMS-receptor complexes in a dose-dependent fashion, demonstrating that the interaction of MBP with the M2 muscarinic receptor is allosteric. This effect of MBP suggests that it may function as an endogenous allosteric inhibitor of agonist binding to the M2 muscarinic receptor. Inhibition of [3H]NMS binding by MBP was reversible by treatment with heparin, which binds and neutralizes MBP. Eosinophil peroxidase (EPO) also inhibited specific binding of [3H]NMS to M2 receptors but not to M3 receptors and inhibited atropine-induced dissociation of [3H]NMS-receptor complexes. On a molar basis, EPO is less potent than MBP. Neither eosinophil cationic protein nor eosinophil-derived neurotoxin affected binding of [3H]NMS to M2 receptors. Thus both MBP and EPO are selective allosteric antagonists at M2 receptors. The effects of these proteins may be important causes of M2 receptor dysfunction and enhanced vagally mediated bronchoconstriction in asthma.

Original languageEnglish (US)
Pages (from-to)1314-1318
Number of pages5
JournalJournal of Clinical Investigation
Volume91
Issue number4
StatePublished - Apr 1993
Externally publishedYes

Fingerprint

Muscarinic M2 Receptors
Eosinophil Peroxidase
Proteins
Atropine
Eosinophil-Derived Neurotoxin
N-Methylscopolamine
Eosinophil Cationic Protein
human PRG2 protein
Bronchoconstriction
Membranes
Submandibular Gland
Eosinophils
Protein Binding
Heparin
Asthma

Keywords

  • Airways
  • Asthma
  • Heparin
  • Parasympathetic nervous system
  • Pulmonary

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. / Jacoby, David; Gleich, Gerald J.; Fryer, Allison.

In: Journal of Clinical Investigation, Vol. 91, No. 4, 04.1993, p. 1314-1318.

Research output: Contribution to journalArticle

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