Which phosphodiesterase can decrease cardiac effects of 5-HT 4 receptor activation in transgenic mice?

摘要: Serotonin (5-hydroxy-tryptamine, 5-HT) exerted concentration-dependent positive inotropic effects or chronotropic in transgenic (TG) mice which overexpress the human 5-HT4a receptor heart but not littermate wild-type (WT) mice. These and are thought to be mediated by cyclic adenosine 3′,5′-monophosphate (cAMP) TG cardiomyocytes. To determine whether these antagonized endogenous phosphodiesterases (PDEs), of 5-HT were tested additional presence PDE inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA) (1 μM, a PDE2 inhibitor) cilostamide PDE3 inhibitor), rolipram (0.1 μM 1 μM, PDE4 their combinations. For comparison, 3-isobutyl-1-methylxanthine (IBMX), an unspecific inhibitor, was investigated. The use 10 μM IBMX, combination (1 μM) EHNA (1 μM), (0.1 μM) each increased potency elevate force contraction mice, increase beating rate This indicates that regulate In contrast, alone, decreased summary, our present data suggest effect does involve activities, whereas basal diminished activity PDE4. Phosphorylation PDE4, when is inhibited, might enhance