Process for screening substances capable of modulating a receptor-dependent cellular signal transmission path

A process for screening a test substance for the ability of the test substance to modulate a receptor-dependent signal transduction pathway in a human or animal cell, wherein said modulation affects the adenylate cyclase signal transduction pathway initiated by a receptor coupled to the signal transduction pathway, comprising

• 1) incubating test mammalian cells with the test substance,
• wherein said test mammalian cells are:
• (a) transformed with a recombinant DNA molecule comprising a reporter gene operably linked to a DNA molecule having a regulatory sequence which responds to a change in concentration of cAMP;
• and
• (b) transformed with a recombinant DNA molecule comprising a sequence which codes for a receptor protein which is coupled functionally to the adenylate cyclase effector system and wherein said mammalian cells express the receptor protein encoded by the recombinant DNA molecule;
• 2) incubating control mammalian cells with said test substance, wherein said control cells are transformed with a recombinant DNA molecule comprising said reporter gene operably linked to a DNA molecule having a regulatory sequence which responds to a change in concentration of cAMP, wherein the same reporter gene and operably controlled regulatory sequence is used in both test and control cells;
• 3) measuring the concentration of said reporter gene product in said control cells and in said test cells;
• 4) comparing the concentration of said reporter gene product in said control cells to the concentration of said reporter gene product in said test cells;
• 5) incubating further control mammalian cells with said test substance, wherein said further control mammalian cells are transformed with a recombinant DNA molecule comprising a reporter gene operably linked to a DNA molecule having a regulatory sequence which responds to a change in concentration of IP.sub.3 and DAG brought about by the modulation of phospholipase activity in said mammalian cells;
• 6) measuring the concentration of said reporter gene product in said further control cells and in said test cells;
• and
• 7) comparing the concentration of said reporter gene product in said further control cells to the concentration of said reporter gene product in said test cells.