Further investigations on the influence of protein phosphatases on the signaling of muscarinic receptors in the atria of mouse hearts.
Naunyn Schmiedebergs Arch Pharmacol
; 397(8): 5731-5743, 2024 08.
Article
em En
| MEDLINE
| ID: mdl-38308688
ABSTRACT
The vagal regulation of cardiac function involves acetylcholine (ACh) receptor activation followed by negative chronotropic and negative as well as positive inotropic effects. The resulting signaling pathways may include Gi/o protein-coupled reduction in adenylyl cyclase (AC) activity, direct Gi/o protein-coupled activation of ACh-activated potassium current (IKACh), inhibition of L-type calcium ion channels, and/or the activation of protein phosphatases. Here, we studied the role of the protein phosphatases 1 (PP1) and 2A (PP2A) for muscarinic receptor signaling in isolated atrial preparations of transgenic mice with cardiomyocyte-specific overexpression of either the catalytic subunit of PP2A (PP2A-TG) or the inhibitor-2 (I2) of PP1 (I2-TG) or in double transgenic mice overexpressing both PP2A and I2 (DT). In mouse left atrial preparations, carbachol (CCh), cumulatively applied (1 nM-10 µM), exerted at low concentrations a negative inotropic effect followed by a positive inotropic effect at higher concentrations. This biphasic effect was noted with CCh alone as well as when CCh was added after ß-adrenergic pre-stimulation with isoprenaline (1 µM). Whereas the response to stimulation of ß-adrenoceptors or adenosine receptors (used as controls) was changed in PP2A-TG, the response to CCh was unaffected in atrial preparations from all transgenic models studied here. Therefore, the present data tentatively indicate that neither PP2A nor PP1, but possibly other protein phosphatases, is involved in the muscarinic receptor-induced inotropic and chronotropic effects in the mouse heart.
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MEDLINE
Assunto principal:
Carbacol
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Camundongos Transgênicos
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Transdução de Sinais
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Receptores Muscarínicos
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Proteína Fosfatase 1
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Proteína Fosfatase 2
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Átrios do Coração
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article