Mammal heart tissue has long been assumed to be the exclusive domain of the M(2) 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 M(2) 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 M(1) muscarinic receptors using MT7 toxin, subtype-specific immunoprecipitation experiments and determination of phospholipase C activity. We also attempted to block M(1)-M(4) receptors using co-treatment with MT7 and AQ-RA 741. Our results show that only the M(2) 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 M(2), with the majority of these belonging to the M(1) subtype. We were also able to detect a marginal fraction (6 +/- 2%) of receptors that, based on other findings, belong mainly to the M(5) muscarinic receptors. Co-treatment with MT7 and AQ-RA 741 was not a suitable tool for blocking of M(1)-M(4) receptors and can not therefore be used as a method for M(5) muscarinic receptor detection in substitution to crude venom. These results provide further evidence of the expression of the M(1) 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 M(5) muscarinic receptors but not to that of the M(3) receptors.

• MeSH
• exprese genu MeSH
• fosfolipasy typu C metabolismus   MeSH
• kompetitivní vazba MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• receptor muskarinový M1 účinky léků   metabolismus   MeSH
• receptor muskarinový M2 účinky léků   metabolismus   MeSH
• receptor muskarinový M3 účinky léků   metabolismus   MeSH
• receptor muskarinový M5 účinky léků   metabolismus   MeSH
• receptory muskarinové účinky léků   metabolismus   MeSH
• srdeční komory účinky léků   metabolismus   MeSH
• srdeční síně účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfolipasy typu C MeSH
• receptor muskarinový M1 MeSH
• receptor muskarinový M2 MeSH
• receptor muskarinový M3 MeSH
• receptor muskarinový M5 MeSH
• receptory muskarinové MeSH

Glucocorticoids affect the expression and density of neurotransmitter receptors in many tissues but data concerning the heart are contradictory and incomplete. We injected rats with hydrocortisone for 1-12 days and measured the densities of cardiac muscarinic receptors, alpha(1)-, beta(1)- and beta(2)-adrenoceptors and propranolol-resistant binding sites (formerly assumed to be the putative beta(4)-adrenoceptor). Some aspects of intracellular signalling were also evaluated: we measured adenylyl cyclase activity (basal, isoprenaline- and forskolin-stimulated and carbachol-inhibited), the coupling between muscarinic receptors and G proteins and basal and isoprenaline-stimulated heart rate. The density of cardiac muscarinic receptors increased (in both the atria and the ventricles). The density of beta(1)-adrenoceptors increased in the atria and was little changed in the ventricles. The density of beta(2)-adrenoceptors increased in both the atria and the ventricles. The number of alpha(1)-adrenoceptors decreased initially, followed by a transient increase in the atria and did not change in the ventricles. The density of propranolol-resistant binding sites first increased and then diminished in the atria and did not change in the ventricles. Although there were noticeable changes in receptor densities, the stimulatory and inhibitory effects on adenylyl cyclase, basal and isoprenaline-stimulated heart rate and the coupling between muscarinic receptors and G proteins were not significantly altered. This may indicate that changes in receptor densities might be one of the mechanisms maintaining stable functional output.

• MeSH
• adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• alfa-1-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• beta blokátory farmakologie   MeSH
• beta-1-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• beta-2-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• beta-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• glukokortikoidy aplikace a dávkování   farmakologie   MeSH
• hydrokortison aplikace a dávkování   farmakologie   MeSH
• injekce subkutánní MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• potkani Wistar MeSH
• propanolaminy farmakologie   MeSH
• propranolol farmakologie   MeSH
• radioligandová zkouška MeSH
• receptory muskarinové účinky léků   metabolismus   fyziologie   MeSH
• signální transdukce účinky léků   MeSH
• srdeční komory účinky léků   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adrenergic beta-4 receptor MeSH Prohlížeč
• adrenergní receptory MeSH
• alfa-1-adrenergní receptory MeSH
• beta blokátory MeSH
• beta-1-adrenergní receptory MeSH
• beta-2-adrenergní receptory MeSH
• beta-adrenergní receptory MeSH
• CGP 12177 MeSH Prohlížeč
• glukokortikoidy MeSH
• hydrokortison MeSH
• propanolaminy MeSH
• propranolol MeSH
• receptory muskarinové MeSH