THE recently cloned rat mu opiate receptor cDNA has been expressed in
COS and Chinese hamster ovary (CHO) cells to examine the coupling of t
his receptor to G-protein linked second messenger systems and examine
possible coupling to multiple second messenger systems. Morphine (1 mu
M) reduced both forskolin-stimulated cAMP levels and IP3 levels by 20
+/- 5 and 34 +/- 8% respectively in COS and CHO cell cultures express
ing the cloned rat mu receptor cDNA. Both effects could be blocked by
naloxone and Gpp(NH)p. These results represent the first clear represe
ntation of the second messenger system promiscuity possible with a sin
gle cloned opiate receptor.