THE HUMAN CHEMOATTRACTANT COMPLEMENT C5A RECEPTOR INHIBITS CYCLIC-AMPACCUMULATION THROUGH G(I) AND G(Z) PROTEINS

The human C5a receptor is known to signal through G(i) proteins. The a bility of the cloned C5a receptor to inhibit adenylyl cyclase or to st imulate phospholipase C through G(i) proteins was examined in transfec ted cells. Activation of recombinant C5a receptors resulted in the sti mulation of phospholipase C in Ltk(-) cells and inhibition of adenylyl cyclase in 293 cells. Pertussis toxin potently abolished both respons es indicating the involvement of G(i) proteins. Previous studies have shown that G(i)-mediated inhibition of adenylyl cyclase can be similar ly regulated by the pertussis toxin-insensitive G(z). In 293 cells co- transfected with the alpha subunit of G(z), the C5a-mediated inhibitio n of cAMP accumulation became pertussis toxin-resistant, signifying fu nctional coupling between the C5a receptor and G(z). However, G(z) can not substitute for G(i) in the C5a-induced stimulation of phospholipas e C or inhibition of adenylyl cyclase in Ltk(-) cells. (C) 1995 Academ ic Press, Inc.