Key result
CGS 21680C increased cAMP content in guinea pig ventricular cardiomyocytes from 4.3 to 13.0 pmol/mg protein without affecting force of contraction or protein phosphorylation.
The study demonstrates that CGS 21680C increases cAMP in guinea pig ventricular cardiomyocytes without altering contractility or protein phosphorylation, supporting the existence of functionally distinct cAMP compartments.
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Guinea pig data leave open A2-adenosine effects on ventricular contractility; requires validation in other models before clinical consideration.
Effects of a putative A2-adenosine receptor agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamide-adeno sine (CGS 21680C) on force of contraction, protein phosphorylation, cyclic adenosine monophosphate (cAMP) content, and the activity of phosphodiesterase (PDE) isoenzymes in guinea pig ventricular (GPV) preparations were studied. CGS 21680C (1-100 microM) did not affect force of contraction in isolated electrically driven papillary muscles and was ineffective in increasing phosphorylation of phospholamban (PLB) and the inhibitory subunit of troponin (TnI) in [32P]-labeled GPV cardiomyocytes. However, under the same conditions, CGS 21680C (10 microM) increased cAMP content from 4.3 +/- 0.2 to 13.0 +/- 0.6 pmol/mg protein, and this effect was completely abolished by A2-adenosine receptor antagonist 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo-(1,5-c)quinazolin++ +-5-imine (CGS 15943A). CGS 21680C (10 microM) inhibited PDE isoenzymes I, II, III, IV by 7.0, 8.3, 4.7, and 23.2%, respectively. Similarly, rolipram (100 microM), a selective PDE IV inhibitor, increased cAMP content from 4.4 +/- 0.3 to 7.2 +/- 0.3 pmol/mg protein without affecting the phosphorylation state of PLB and TnI. We conclude that CGS 21680C increases cAMP content in GPV cardiomyocytes by activation of adenylyl cyclase or in part by inhibition of PDE IV activity. The increase in cAMP content by CGS 21680C or rolipram is ineffective in increasing phosphorylation of PLB and TnI. These results support the concept of compartments for cAMP or protein kinase A or both in cardiomyocytes that are not coupled to phosphorylation and contractility.
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Boknı́k et al. (1997) studied Guinea pig ventricular preparations. CGS 21680C was evaluated on cAMP content. CGS 21680C increased cAMP content in guinea pig ventricular cardiomyocytes from 4.3 to 13.0 pmol/mg protein without affecting force of contraction or protein phosphorylation.
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