One of the great things about Bach’s organ music is how changes
of a single note in a whole pattern can have rather dramatic
effects on the sound. A unique and potentially very important
similar phenomenon has been discovered recently in the area of
GPCR research. The understanding of the basic process by which
GPCRs transmit signals from the cell exterior to the interior
has seen remarkable advances in the last three decades, but much
still remains to be deciphered. Our knowledge of signaling
responses until now hinged on the action of agonists and
antagonists. Central to this knowledge was the concept of
‘intrinsic efficacy’; according to this concept, there was no
difference between two full agonists for instance, and both of
them would produce the same response irrespective of the
situation. But this understanding failed to explain some
observations. For instance, a full agonist would function as a
partial agonist and even as an inverse agonist under different
circumstances. Several such observations, esp