title: The human chemoattractant complement C5a receptor inhibits cyclic AMP accumulation through Gi and Gz proteins.
abstract: The human C5a receptor is known to signal through Gi proteins. The ability of the cloned C5a receptor to inhibit adenylyl cyclase or to stimulate phospholipase C through Gi proteins was examined in transfected cells. Activation of recombinant C5a receptors resulted in the stimulation of phospholipase C in Ltk- cells and inhibition of adenylyl cyclase in 293 cells. Pertussis toxin potently abolished both responses indicating the involvement of Gi proteins. Previous studies have shown that Gi-mediated inhibition of adenylyl cyclase can be similarly regulated by the pertussis toxin-insensitive GZ. In 293 cells co-transfected with the alpha subunit of GZ, the C5a-mediated inhibition of cAMP accumulation became pertussis toxin-resistant, signifying functional coupling between the C5a receptor and GZ. However, GZ cannot substitute for Gi in the C5a-induced stimulation of phospholipase C or inhibition of adenylyl cyclase in Ltk- cells.
authors.affiliation: Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon.
authors.forename: J K
authors.initials: JK
authors.lastname: Shum
authors.forename: R A
authors.initials: RA
authors.lastname: Allen
authors.forename: Y H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007668:Kidney; D007739:L Cells; D051379:Mice; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D007295:Inositol Phosphates; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011994:Recombinant Proteins; D015936:Complement C5a; D000242:Cyclic AMP; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases