INHIBITION OF ADENYLYL-CYCLASE BY ALPHA-CHEMOKINE IL-8 AND GRO-ALPHA IN CHINESE-HAMSTER OVARY CELLS EXPRESSING R1 AND R2 RECEPTORS

Interleukin-8 (IL-8) and growth-related oncogene protein-alpha (GRO-al pha) belong to a family of a chemokines. The biologic effects of IL-8 are realized by binding to two seven-transmembrane receptors R1 and R2 and that of GRO-alpha by binding to receptor R2. Chinese hamster ovar y (CHO) cells stably expressing R1 and R2 have been used to demonstrat e that the ligand-dependent signaling by both receptors is via the inh ibition of adenylyl cyclase. This inhibition is pertussis toxin sensit ive and could be mediated by G alpha i2, which is present in CHO cells . GRO-alpha inhibits adenylyl cyclase exclusively in CHO-R2 cells, and IL-8 inhibits in both CHO-R1 and CHO-R2 cells. The CAMP status in cel ls is an easy, reliable, quantifiable signal that is amenable to high throughput screening for small molecule analogs.