ADENOSINE A(1) RECEPTOR-INDUCED UP-REGULATION OF PROTEIN-KINASE-C - ROLE OF PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN(S)

Biochemical and pharmacological studies have established that adenosin e modulates protein kinase C (PKC), which plays an important role in t he maintenance of vascular tone. Our earlier studies [Marala and Musta fa. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H271-H277, 1995. Ma rala, R. B., K. Ways, and S. J. Mustafa. Am. J. Physiol. 264 (Heart Ci rc. Physiol. 33): H1465-H1471, 1993] have shown the involvement of ade nosine A(1) receptors and not the Az receptors in the upregulation of PKC in porcine coronary artery. The mechanism(s) by which adenosine up regulates PKC is not yet clearly understood. We now report the increas ed expression of PKC by adenosine Al receptor through an upstream acti vation of pertussis toxin-sensitive G protein(s). Incubation of porcin e coronary artery for 24 h with a relatively specific A(1)-receptor ag onist (2S)-N-6-(2-endo-norbornyl)adenosine (ENBA) elevated the contrac tile responses to endothelin-l by about twofold, probably due to an in creased expression of PKC. Incubation of porcine coronary artery with ENBA also protected against the phorbol 12,13-dibutyrate (PDBu)-induce d depletion of PKC. Inclusion of pertussis toxin in the incubation med ium completely blocked both the upregulatory and the protective effect s of ENBA. Incubation with pertussis toxin did not alter the PKC activ ity as judged by the contractile responses to PDBu. On the contrary, i ncubation of porcine coronary artery with cholera toxin for 24 h did n ot alter any of the ENBA responses (upregulation of PKC and the protec tion against PDBu-induced PKC depletion). Incubation conditions of cor onary arteries with toxins are sufficient to cause ADP ribosylation of respective G proteins as judged by back ADP ribosylation studies. We thus conclude that the upregulation of PKC by adenosine A(1) receptor is through pertussis toxin-sensitive G protein(s).