Original Article

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 378, Issue 1, pp 103-116

First online:

The detection of the non-M2 muscarinic receptor subtype in the rat heart atria and ventricles

  • Jaromir MyslivecekAffiliated withInstitute of Physiology, 1st Faculty of Medicine, Charles University Email author 
  • , Martin KleinAffiliated withInstitute of Physiology, 1st Faculty of Medicine, Charles University
  • , Martina NovakovaAffiliated withInstitute of Physiology, 1st Faculty of Medicine, Charles University
  • , Jan RicnyAffiliated withPrague Psychiatric CentreInstitute of Physiology, Academy of Sciences of the Czech Republic

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Mammal heart tissue has long been assumed to be the exclusive domain of the M2 subtype of muscarinic receptor, but data supporting the presence of other subtypes also exist. We have tested the hypothesis that muscarinic receptors other than the M2 subtype are present in the heart as minor populations. We used several approaches: a set of competition binding experiments with pirenzepine, AFDX-116, 4-DAMP, PD 102807, p-F-HHSiD, AQ-RA 741, DAU 5884, methoctramine and tripinamide, blockage of M1 muscarinic receptors using MT7 toxin, subtype-specific immunoprecipitation experiments and determination of phospholipase C activity. We also attempted to block M1–M4 receptors using co-treatment with MT7 and AQ-RA 741. Our results show that only the M2 subtype is present in the atria. In the ventricles, however, we were able to determine that 20% (on average) of the muscarinic receptors were subtypes other than M2, with the majority of these belonging to the M1 subtype. We were also able to detect a marginal fraction (6 ± 2%) of receptors that, based on other findings, belong mainly to the M5 muscarinic receptors. Co-treatment with MT7 and AQ-RA 741 was not a suitable tool for blocking of M1–M4 receptors and can not therefore be used as a method for M5 muscarinic receptor detection in substitution to crude venom. These results provide further evidence of the expression of the M1 muscarinic receptor subtype in the rat heart and also show that the heart contains at least one other, albeit minor, muscarinic receptor population, which most likely belongs to the M5 muscarinic receptors but not to that of the M3 receptors.


Heart Immunoprecipitation MT7 mamba toxin Muscarinic receptors Non-M2 muscarinic receptor PLC activity