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Which preconditioning‐associated G protein‐coupled receptors are expressed on the sarcolemma?
Author(s) -
Xin Wenkuan,
Cohen Michael V.,
Rich Thomas C.,
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.793.25
Subject(s) - agonist , receptor , chemistry , sarcolemma , patch clamp , biophysics , medicine , endocrinology , dadle , adenosine , microbiology and biotechnology , pharmacology , myocyte , biology , biochemistry , opioid receptor
It has been assumed that G protein‐coupled receptors associated with preconditioning reside on the sarcolemma. We tested that assumption by infecting rabbit ventricular myocytes with adenovirus encoding cyclic nucleotide‐gated channels. Increasing cAMP opens the channel and increases ionic currents measured using whole cell patch clamp. Peak current was determined by exposure of cells to a phosphodiesterase inhibitor cocktail (PDEI) plus 50nM isoproterenol (ISO) at end of experiments. Current after 50nM ISO binding to G s ‐coupled β‐adrenergic receptors was 56±9% of peak. 500nM Bradykinin or 20nM δ‐opioid agonist DADLE reduced ISO current to 19±5 and 11±3% of peak, respectively, indicating activation of these G i ‐coupled receptors. 200nM CCPA and 200nM IB‐MECA, adenosine A 1 and A 3 agonists, respectively, also attenuated responses to ISO with maximal currents of 25±11% and 24±5% of peak. A 2 subtypes are normally G s ‐coupled. Neither 1μM BAY60‐6583, A 2b agonist, nor 300nM CGS21680, A 2a agonist, increased current themselves, but CGS21680 could after PDEI indicating a low level of A 2a . Neither attenuated ISO's current. We conclude that all four G i ‐coupled receptors and the G s ‐coupled A 2a are present but not A 2b . If there really is a role for the A 2b in preconditioning's protection, then the signaling must involve a different cell type in the heart such as vascular smooth muscle. HL‐20648, HL‐74278