Key Points
- To examine the effects of carbachol and the A1-adenosine receptor agonist PIA on myocardial force of contraction and inositol lipid metabolism.
- Evaluated contractile force and inositol phosphate content in electrically driven left auricles and papillary muscles isolated from guinea-pig hearts exposed to carbachol and PIA (0.01–100 μM).
- Assessed receptor mediation by preincubating tissues with the muscarinic antagonist atropine (10 μM) or the A1-adenosine antagonist DPCPX (20 μM).
- Carbachol and PIA produced concentration-dependent negative inotropic effects in auricles; in papillary muscles, PIA had no inotropic effect, whereas high concentrations of carbachol (10–100 μM) elicited a modest positive inotropic effect.
- Both agonists significantly elevated inositol trisphosphate (IP3) at 1 μM with a corresponding reduction in precursor phosphatidylinositol bisphosphate, which was completely blocked by atropine and DPCPX.
- Negative inotropy in auricles preceded IP3 elevation, while PIA increased IP3 in papillary muscles without altering contractile force, demonstrating a dissociation between IP3 production and contractile response.
Structured PICO
PPopulationElectrically driven left auricles and papillary muscles isolated from guinea-pig hearts
IInterventionCarbachol and (-)-N6-phenylisopropyladenosine (PIA) (0.01-10 microM)
OOutcomeForce of contraction and inositol lipid metabolism (IP3 and PIP2 content)surrogate
The study questions the role of IP3 as an endogenous regulator of myocardial force of contraction, as PIA increased IP3 without a corresponding inotropic effect.