ABSTRACT

The receptors responsible for odorant discrimination were first cloned in 1991 by Linda Buck and Richard Axel (Buck and Axel 1991). A series of physiological and biochemical experiments performed during the mid-1980s indicated that odorant activation of olfactory sensory neurons was mediated by a G-protein-dependent pathway, which led to activation of adenylyl cyclase, increases in intracellular concentrations of cyclic adenosine monophosphate (cAMP), activation of cyclic nucleotide-gated channels, and neuron depolarization (Firestein et al. 1991; Lowe et al. 1989; Nakamura and Gold 1987; Pace et al. 1985; Sklar et al. 1986; see also Chapter 8). The subsequent cloning of olfactory-specific genes coding for a Gα protein (Gαolf) (Jones and Reed 1989) and for a cAMP-gated channel (Dhallan et al. 1990) further strengthened the involvement of cAMP in odorant signal transduction. These experiments strongly indicated that the odorant receptors (ORs) should be G-protein-coupled receptors (GPCRs).