Olfactory Transduction Studied with Caged Cyclic Nucleotides

Abstract

Although olfaction has captured the attention of scientists and philosophers alike for most of recorded history, it is only during the past twenty years that our present understanding of odor detection (transduction) has begun to emerge. In 1972, Kurihara and Koyama [1] demonstrated that the olfactory epithelium contains a high concentration of adenylyl cyclase, the enzyme that synthesizes cyclic AMP (adenosine monophosphate). Based on this observation, they proposed that the intracellular messenger cyclic AMP plays an important role in olfactory transduction. In 1973 Minor and Sakina [2] reported that dibutyryl cyclic AMP induced an electroolfactogram (EOG) response similar to that evoked by odorants, thus providing the first electrophysiological evidence that cyclic AMP is an excitatory messenger in olfactory transduction. Similar experiments were reported by Menevse et al. in 1977 [3]. The first biochemical evidence in support of the excitatory hypothesis was provided in 1985 by Pace et al. [4], who showed that the olfactory adenylyl cyclase can be stimulated by odorants. Perhaps more importantly, they showed that adenylyl cyclase activation was GTP-dependent, suggesting that olfactory receptor cells contain a G-protein-linked enzymatic cascade similar to those that mediate signal transduction in a variety of other cell types. In 1987, Nakamura and Gold [5] discovered a likely target for cyclic AMP, an ion channel that was activated directly by this intracellular messenger. This ion channel is quite similar to the cyclic guano-sine monophosphate- (GMP-) gated channel that mediates visual transduction in photoreceptors [6], further indicating a close ·relationship between olfactory transduction and other signal transduction mechanisms. The final link between olfactory and other signal transduction mechanisms was provided by the cloning of a very large family of olfactory receptor proteins by Buck and Axel in 1991, based on sequence homology with other G-protein-linked receptor proteins [7].