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

The human C5a receptor is known to signal through G(i) proteins. The ability of the cloned C5a receptor to inhibit adenylyl cyclase or to stimulate phospholipase C through G(i) 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 G(i) proteins. Previous studies have shown that G(i)-mediated inhibition of adenylyl cyclase can be similarly regulated by the pertussis toxin-insensitive G(z). In 293 cells co-transfected with the alpha subunit of G(z), the C5a-mediated inhibition of cAMP accumulation became pertussis toxin-resistant, signifying functional coupling between the C5a receptor and G(z). However, G(z) cannot substitute for G(i) in the C5a-induced stimulation of phospholipase C or inhibition of adenylyl cyclase in Ltk(-) cells. (C) 1995 Academic Press, Inc.