Premium
Adenosine A 2b receptors unexpectedly activate cardioprotective kinases through G i rather than G s
Author(s) -
Kuno Atsushi,
Walker Sheree,
Dost Turhan,
Cohen Michael V.,
Downey James M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1026.4
Subject(s) - pertussis toxin , kinase , protein kinase c , receptor , agonist , adenosine , protein kinase b , adenosine receptor , microbiology and biotechnology , g protein coupled receptor , biology , chemistry , signal transduction , endocrinology , pharmacology , biochemistry , g protein
We reported that A 2b receptors in the heart couple to the survival kinases Akt and ERK and that in preconditioned heart the A 2b receptor′s sensitivity to adenosine is increased by PKC so endogenous adenosine becomes protective. We explored the behavior of these receptors in a simple model of human embryonic kidney cells stably transfected with human A 2b receptors. Incubation of these cells with the A 2b ‐potent agonist 5′‐(N‐ethylcarboxamido) adenosine (NECA) caused a dose‐dependent activation of Akt and ERK as determined by western blotting with phospho‐specific antibodies. NECA also increased cAMP consistent with the previously reported G s ‐coupling of A 2b receptors. The A 2b ‐selective antagonist MRS1754 blocked NECA′s ability to activate the kinases confirming an A 2b mechanism. Activation of PKC with phorbol 12‐myristate 13‐acetate increased the sensitivity to NECA 10‐fold as compared to cells in which PKC was blocked with chelerythrine thus confirming PKC′s effect on receptor signaling. However, when G s was inhibited with cholera toxin or the G s ‐antagonist NF449, the ability of NECA to activate the kinases was actually enhanced. Pertussis toxin abolished the ability of either NECA or the highly selective A 2b agonist BAY60‐6583 to activate the kinases indicating that the A 2b receptor activates the kinases by a G i ‐rather than a G s ‐coupled mechanism. Supported by HL20648