Identification of rat brain muscarinic M4 receptors coupled to cyclic AMP using the selective antagonist muscarinic toxin 3

Maria C. Olianas, Abdu Adem, Evert Karlsson, Pierluigi Onali

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

In membranes of olfactory tubercle and striatum, the selective muscarinic M4 receptor antagonist muscarinic toxin 3 completely antagonized the acetylcholine-induced inhibition of forskolin- and dopamine D1 receptor-stimulated cyclic AMP formation with K(i) values of 7 and 4 nM, respectively. In olfactory bulb, where acetylcholine stimulated basal adenylyl cyclase activity and inhibited forskolin-stimulated enzyme activity, muscarinic toxin 3 caused a partial antagonism of both acetylcholine effects with high potencies (K(i) values=4-6 nM). In frontal cortex, muscarinic toxin 3 counteracted the acetylcholine-induced potentiation of corticotropin-releasing hormone-stimulated cyclic AMP with a K(i) of 58 nM, which is close to the toxin affinity for the muscarinic M1 receptor. In the same brain region, the acetylcholine inhibition of forskolin-stimulated enzyme activity was not affected by muscarinic toxin 3. In microdissected regions of the hippocampus, a significant portion (33-48%) of the acetylcholine inhibition of forskolin-stimulated adenylyl cyclase activity was blocked by muscarinic toxin 3 with K(i) values (6-8 nM) consistent with the involvement of muscarinic M4 receptors. These data show that muscarinic toxin 3 discriminates between adenylyl cyclase-coupled muscarinic receptors and demonstrate the utility of the toxin in identifying the relative contribution by the muscarinic M4 receptor subtype. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)235-242
Number of pages8
JournalEuropean Journal of Pharmacology
Volume357
Issue number2-3
DOIs
Publication statusPublished - Sep 18 1998
Externally publishedYes

Keywords

  • Adenylyl cyclase
  • Brain, rat
  • Muscarinic receptor subtype
  • Muscarinic toxin 3

ASJC Scopus subject areas

  • Pharmacology

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