ADENOSINE-ANALOGS PREVENT PHORBOL ESTER-INDUCED PKC DEPLETION IN PORCINE CORONARY-ARTERY VIA A(1) RECEPTOR

This study was undertaken to determine the adenosine receptor involved in the modulation of protein kinase C (PKC) in porcine coronary artery. Endothelium-denuded arterial rings were incubated with phorbol 12,13-dibutyrate (PDBu) in the presence or absence of adenosine receptor agonists and antagonists for 24 h. After incubation, contractile responses to endothelin-l (ET-1) were compared in various treatment groups. Arterial rings incubated with PDBu alone failed to produce significant contractions in response to ET-1. (2s)-N-6-[2-endo-norbornyl]adenosine (ENBA), an Al-receptor agonist, attenuated the PDBu-induced blunting of the ET-1 contractions. Incubation with ENBA alone elevated ET-1 contractility by about twofold. Inclusion of A(1)-receptor antagonists completely blocked both effects of ENBA: protection against PDBu and increase in ET-1 contractility. On the contrary, arterial rings incubated with the A(1)-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680) did not show significant alteration of the ET-1 contractility when incubated with CGS-21680 alone or in combination with PDBu. Inclusion of A(2)-receptor antagonist in combination with CGS-21680 mimicked the effects of ENBA alone, i.e., protected against PDBu and enhanced ET-1 contractions. Measurement of PKC activities in arteries indicated that exposure to ENBA caused a twofold increase in the enzyme activity, whereas exposure to CGS-21680 had no significant effect on PKC activity. Adenosine analogues caused an accumulation of PKC through the activation of A(1)- but not A(2)-adenosine receptors. These results indicate that the modulation of PKC by adenosine analogues is mediated through A(1)-adenosine receptors in the coronary artery.