Differential regulation of cAMP by endogenous versus transfected formylpeptide chemoattractant receptors: implications for Gi-coupled receptor signaling.
Endogenous neutrophil formylpeptide receptors do not inhibit adenylylcyclase activation. The ability of a cloned and transfected human formylpeptide receptor to mediate the inhibition of adenylylcyclase was assessed in the human embryonic kidney 293 TSA cell line. Inclusion of 1 microM fMetLeuPhe resulted in a ca. 50% inhibition of isoproterenol-stimulated cAMP in transfected cells. Activation of adenylylcyclase by isoproterenol was inhibited ca. 30% by fMetLeuPhe in membranes prepared from transfected cells but not in membranes prepared from neutrophils. Prior treatment of transfected cells with pertussis toxin abrogated the inhibitory effect of fMetLeuPhe. These data indicate that factors in addition to the primary structure of the formylpeptide receptor govern its transductional activities.
Uhing
R J
RJ
Department of Pathology, Duke University Medical Center, Durham, NC 27710.
Gettys
T W
TW
Tomhave
E
E
Snyderman
R
R
Didsbury
J R
JR
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism*; D004622:Embryo, Mammalian; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008566:Membranes / Q000378:metabolism; D037342:Pertussis Toxin; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002118:Calcium