| Autor: |
Dobson Jr., James G., Shea, Lynne G., Fenton, Richard A. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Dec2008, Vol. 295 Issue 6, pH2364-H2372, 9p, 1 Chart, 8 Graphs |
| Abstrakt: |
The adenosine A2A receptor (A2AR) enhances cardiac contractility, and the adeno- sine A1R receptor (A1R) is antiadrenergic by reducing the adrenergic ~ receptor (I3iR)-elicited increase in contractility. In this study we compared the A2AR-, A1R-, and 131R-elicited actions on isolated rat ventricular myocytes in terms of Ca transient and contractile re- sponses involving PKA and PKC. Stimulation of A2AR with 2 p~M (-.~EC50) CGS-21680 (CGS) produced a 17-28% increase in the Ca transient ratio (CTR) and maximum velocities (Vm~,,~) of transient ratio increase (+MVT) and recovery (-MVT) but no change in the time-to-50% recovery (TTR). CGS increased myocyte sarcomere shortening (MSS) and the maximum velocities of shortening (+MVS) and relaxation (-MVS) by 31-34% with no change in time-to-50% relengthening (TTL). ~1R stimulation using 2 nM (-~EC50) isopro- terenol (Iso) increased CTR, +MVT, and -MVT by 67-162% and decreased TTR by 43%. Iso increased MSS, +MVS, and -MVS by 153-174% and decreased TI'L by 31%. The A2AR and ~31R Ca transient and contractile responses were not additive. The PKA inhibitor Rp-adenosine 3' ,5 `-cyclic monophosphorothioate triethyla- monium salt prevented both the CGS- and Iso-elicited contractile responses. The PKC inhibitors chelerythrine and KJE1-l peptide (PKCe specific) prevented the antiadrenergic action of A1R but did not influence A2AR-mediated increases in contractile variables. The findings suggest that cardiac A2AR utilize cAMPIPKA like 31R, but the Ca transient and contractile responses are less in magnitude and not equally affected. Although PKC is important in the ~ R antiad- renergic action, it does not seem to play a role in A2AR-elicited Ca transient and contractile events. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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