Effects of adenosine analogues on contractile response and CAMP content in guinea-pig isolated ventricular myocytes
- 1 December 1989
- journal article
- research article
- Published by Springer Nature in Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie
- Vol. 340 (6) , 689-695
- https://doi.org/10.1007/bf00717746
Abstract
Summary In the present study the effects of adenosine analogues were investigated on cAMP content and contractile response in guinea-pig ventricular myocytes. The adenosine analogues (−)-N6-phenylisopropyladenosine (R-PIA), 5′-N-ethylcarboxamideadenosine (NECA) and (+)-N6-phenyl-isopropyladenosine (S-PIA) in the presence of 0.01 μmol/l isoprenaline reduced contractile response concentration-dependently. R-PIA and NECA were about equipotent (IC25: 0.01 μmol/l and 0.039 μmol/l respectively), while S-PIA was less potent (IC25: 0.6 μmol/l). Isoprenaline stimulated cAMP content was reduced by R-PIA (IC25: 0.004 μmol/l) and with lower potency by S-PIA (IC25: 0.15 μmol/l) but the extent of reduction of cAMP by R-PIA and S-PIA (to 55% and 64% respectively) was less than the reduction of contractile response (to 26% and 55% respectively). This suggests that the effects of R- and S-PIA on contractile response are only in part due to a reduction in cAMP content. In addition, NECA did not decrease cAMP content but decreased contractile response to the same extent as R-PIA. Similar results were obtained in the presence of the phosphodiesterase inhibitor Ro 20-1724. Time course studies revealed that the effects of R-PIA (1 μmol/l) on cAMP content and contractile response coincided reaching steady state after 5 min and remained stable thereafter. The effects of NECA (1 µmol/l) on contractility also reached steady state within 5 min, whereas it did not change cAMP content. It is concluded that the reduction of contractility by adenosine analogues in the presence of isoprenaline can only in part be explained by a reduction of cAMP content. It is suggested that a cAMP-independent effect, possibly an activation of phosphatases, might be involved additionally.Keywords
This publication has 38 references indexed in Scilit:
- Contractile responses of isolated adult rat and rabbit cardiac myocytes to isoproterenol and calciumJournal of Molecular and Cellular Cardiology, 1988
- Evidence for adenylate cyclase-coupled A1-adenosine receptors on ventricular cardiomyocytes from adult rat and dog heartLife Sciences, 1987
- The role of endogenous noradrenaline in the beta-blocker withdrawal phenomenon — studies with culture heart cellsJournal of Molecular Medicine, 1987
- Single adult rabbit and rat cardiac myocytes retain the Ca2+- and species-dependent systolic and diastolic contractile properties of intact muscle.The Journal of general physiology, 1986
- Cardiac sarcolemmal purity is essential for the verification of adenylate cyclase inhibition via A1-adenosine receptorsNaunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1986
- Culturing of calcium stable adult cardiac myocytesJournal of Molecular and Cellular Cardiology, 1982
- Enzymes of the Renin-Angiotensin System and their InhibitorsAnnual Review of Biochemistry, 1982
- ADENOSINE REGULATES VIA TWO DIFFERENT TYPES OF RECEPTORS, THE ACCUMULATION OF CYCLIC AMP IN CULTURED BRAIN CELLSJournal of Neurochemistry, 1979
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976