The M2 muscarinic receptors are essential for signaling in the heart left ventricle during restraint stress in mice
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- Klíčová slova
- Adenylyl cyclase, heart, muscarinic receptors, phospholipase C, protein kinase C, stress,
- MeSH
- adenylátcyklasy metabolismus MeSH
- AMP cyklický metabolismus MeSH
- exprese genu MeSH
- fosfolipasy typu C metabolismus MeSH
- fyzické omezení MeSH
- myši knockoutované MeSH
- myši MeSH
- proteinkinasa C metabolismus MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus MeSH
- psychický stres genetika patofyziologie MeSH
- receptor muskarinový M2 genetika MeSH
- receptory muskarinové genetika MeSH
- signální transdukce MeSH
- srdce MeSH
- srdeční frekvence genetika fyziologie MeSH
- srdeční komory metabolismus MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenylátcyklasy MeSH
- AMP cyklický MeSH
- fosfolipasy typu C MeSH
- proteinkinasa C MeSH
- proteinkinasy závislé na cyklickém AMP MeSH
- receptor muskarinový M2 MeSH
- receptory muskarinové MeSH
- synthasa oxidu dusnatého MeSH
We hypothesized that muscarinic receptors (MRs) in the heart have a role in stress responses and thus investigated changes in MR signaling (gene expression, number of receptors, adenylyl cyclase (AC), phospholipase C (PLC), protein kinase A and C (PKA and PKC) and nitric oxide synthase [NOS]) in the left ventricle, together with telemetric measurement of heart rate (HR) in mice (wild type [WT] and M2 knockout [KO]) during and after one (1R) or seven sessions (7R) of restraint stress (seven mice per group). Stress decreased M2 MR mRNA and cell surface MR in the left ventricle in WT mice. In KO mice, 1R, but not 7R, decreased surface MR. Similarly, AC activity was decreased in WT mice after 1R and 7R, whereas in KO mice, there was no change. PLC activity was also decreased after 1R in WT and KO mice. This is in accord with the concept that cAMP is a key player in HR regulation. No change was found with stress in NOS activity. Amount of AC and PKA protein was not changed, but was altered for PKC isoenzymes (PKCα, β, γ, η and ϵ (increased) in KO mice, and PKCι (increased) in WT mice). KO mice were more susceptible to stress as shown by inability to compensate HR during 120 min following repeated stress. The results imply that not only M2 but also M3 are involved in stress signaling and in allostasis. We conclude that for a normal stress response, the expression of M2 MR to mediate vagal responses is essential.
Citace poskytuje Crossref.org