Adenosine a1 receptor induced up regulation of protein kinase c:
involvement of pertussis toxin sensitive g-protein(s).
Marala, Ravi B., and S. Jamal Mustafa.
DEPARTMENT OF PHARMACOLOGY, SCHOOL OF MEDICINE, EAST CAROLINA
UNIVERSITY, GREENVILLE, NC 27858
APStracts 2:0214H, 1995.
Biochemical and pharmacological studies have established that
adenosine modulates protein kinase C (PKC), which plays an important
role in the maintenance of vascular tone. Our earlier studies (18,20)
have shown the involvement of adenosine A1 receptors and not the A2
receptors in the upregulation of PKC in porcine coronary artery. The
mechanism(s) by which adenosine upregulates PKC is not yet clearly
understood. We now report the increased expression of PKC by
adenosine A1 receptor through an upstream activation of pertussis
toxin sensitive G-protein(s). Incubation of porcine coronary artery
for 24 hours with a relatively specific A1 receptor agonist (2s)-N6
-[2-endo-norbornyl] adenosine (ENBA) elevated the contractile
responses to endothelin-1 by about two folds, probably due to an
increased expression of PKC. Incubation of porcine coronary artery
with ENBA also protected against the phorbol ester (PDBu) induced
depletion of PKC. Inclusion of pertussis toxin in the incubation
medium completely blocked both the upregulatory and the protective
effects of ENBA. Incubation with pertussis toxin did not alter the
PKC activity as judged by the contractile responses to PDBu. On the
contrary, incubation of porcine coronary artery with cholera toxin
for 24 hours did not alter any of the ENBA responses (upregulation of
PKC and the protection against PDBu induced PKC depletion).
Incubation conditions of coronary arteries with toxins is 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 A1 receptor is through pertussis toxin sensitive G
-protein(s).
Received 17 August 1994; accepted in final form 12 May 1995.
APS Manuscript Number H742-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.