Key Points
- To determine whether A1-adenosine receptor-mediated inhibition of adenylate cyclase is altered in failing compared to nonfailing human ventricular myocardium.
- Analyzed crude particulate membrane preparations derived from 12 nonfailing and 12 failing human left ventricles.
- Generated dose-response curves using the selective A1-adenosine receptor agonist R-phenylisopropyl-adenosine (R-PIA) under conditions optimized for maximal inhibition.
- Quantitated alpha Gi levels via pertussis toxin-catalyzed ADP-ribosylation and assessed adenylate cyclase catalytic subunit responsiveness to fluoride, forskolin, and manganese.
- Maximal R-PIA-mediated inhibition (31.1 ± 2.6 vs 30.2 ± 1.6 pmol cAMP/min/mg) and ED50 values (1.28 ± 0.10 vs 1.36 ± 0.08 × 10⁻⁷ M) did not differ between nonfailing and failing hearts.
- Inhibitory G protein alpha Gi was significantly higher in failing hearts compared to nonfailing hearts (132.7 ± 3.4 vs 105.7 ± 5.8 optical density units, p < 0.003).
- Basal adenylate cyclase activity under G protein-evaluating conditions was significantly decreased in failing hearts (4.5 ± 0.4 vs 7.8 ± 0.8 pmol cAMP/min/mg, p < 0.005).
Structured PICO
PPopulationCrude particulate preparations derived from 12 nonfailing and 12 failing human left ventricles
IInterventionA1-adenosine receptor agonist R-phenylisopropyl-adenosine (R-PIA)
CComparatorNonfailing human left ventricles
OOutcomeA1-adenosine receptor inhibition of adenylate cyclase (maximal R-PIA-mediated inhibition)surrogate
Despite an increase in the inhibitory G protein alpha Gi in failing human hearts, A1-adenosine receptor inhibition of adenylate cyclase remains unaltered compared to nonfailing hearts.