Beschreibung:
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<jats:list-item><jats:p>Muscarinic receptors (M‐receptors) in the mammalian heart are predominantly of the M<jats:sub>2</jats:sub>‐subtype. The aim of this study was to find out whether there might exist an additional myocardial non‐M<jats:sub>2</jats:sub>‐receptor.</jats:p></jats:list-item>
<jats:list-item><jats:p>For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol‐induced [<jats:sup>3</jats:sup>H]‐inositol phosphate (IP) formation, and its inhibition by M‐receptor antagonists.</jats:p></jats:list-item>
<jats:list-item><jats:p>Carbachol (10<jats:sup>−7</jats:sup>–10<jats:sup>−3</jats:sup> mol l<jats:sup>−1</jats:sup>) increased IP‐formation (maximal increase: 14±3% above basal, <jats:italic>n</jats:italic>=6). This increase was significantly enhanced by pretreatment with pertussis toxin (PTX, 250 ng ml<jats:sup>−1</jats:sup> for 20 h): maximal increase was 31±5%, pEC<jats:sub>50</jats:sub>‐value was 5.08±0.33 (<jats:italic>n</jats:italic>=6).</jats:p></jats:list-item>
<jats:list-item><jats:p>In PTX‐pretreated cardiomyocytes 100 μmol l<jats:sup>−1</jats:sup> carbachol‐induced IP‐formation was inhibited by atropine (pK<jats:sub>i</jats:sub>‐value: 8.89±0.10) and by the M<jats:sub>3</jats:sub>‐receptor antagonist darifenacin (pK<jats:sub>i</jats:sub>‐value: 8.67±0.23) but was not significantly affected by the M<jats:sub>1</jats:sub>‐receptor antagonist pirenzepine (1 μmol l<jats:sup>−1</jats:sup>) or the M<jats:sub>2</jats:sub>‐receptor antagonists AF‐DX 116 and himbacine (1 μmol l<jats:sup>−1</jats:sup>).</jats:p></jats:list-item>
<jats:list-item><jats:p>In conclusion, in adult rat cardiomyocytes there exists an additional, non‐M<jats:sub>2</jats:sub>‐receptor, that is coupled to activation of the phospholipase C/IP<jats:sub>3</jats:sub>‐pathway; this receptor is very likely of the M<jats:sub>3</jats:sub>‐subtype.</jats:p></jats:list-item>
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</jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2003) <jats:bold>138</jats:bold>, 156–160. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0704997">10.1038/sj.bjp.0704997</jats:ext-link></jats:p>