The mechanism of the sense of smell has long been a subject for theory and speculation. More recently, the notion of odorant recognition by stereospecific protein receptors has gained wide acceptance, but the receptor molecules remained elusive. The recognition molecules are believed to be quite diverse, which would partly explain the unusual difficulties encountered in their isolation by conventional ligand-binding techniques. An alternative approach would be to probe the receptors through transductory components that may be common to all receptor types. Here we report the identification of one such transductory molecular component. This is an odorant-sensitive adenylate cyclase, present in very large concentrations in isolated dendritic membranes of olfactory sensory neurones. Odorant activation of the enzyme is ligand and tissue specific, and occurs only in the presence of GTP, suggesting the involvement of receptor(s) coupled to a guanine nucleotide binding protein (G-protein). The olfactory G-protein is independently identified by labelling with bacterial toxins, and found to be similar to stimulatory G-proteins in other systems. Our results suggest a role for cyclic nucleotides in olfactory transduction, and point to a molecular analogy between olfaction and visual, hormone and neurotransmitter reception. Most importantly, the present findings reveal new ways to identify and isolate olfactory receptor proteins.

Sucrose and other saccharides, which produce an appealing taste in rats, were found to significantly stimulate the activity of adenylate cyclase in membranes derived from the anterior-dorsal region of rat tongue. In control membranes derived from either tongue muscle or tongue non-sensory epithelium, the effect of sugars on adenylate cyclase activity was either much smaller or absent. Sucrose enhanced adenylate cyclase activity in a dose-related manner, and this activation was dependent on the presence of guanine nucleotides, suggesting the involvement of a GTP-binding protein ('G-protein'). The activation of adenylate cyclase by various mono- and di-saccharides correlated with their electrophysiological potency. Among non-sugar sweeteners, sodium saccharin activated the enzyme, whereas aspartame and neohesperidin dihydrochalcone did not, in correlation with their sweet-taste effectiveness in the rat. Sucrose activation of the enzyme was partly inhibited by Cu2+ and Zn2+, in agreement with their effect on electrophysiological sweet-taste responses. Our results are consistent with a sweet-taste transduction mechanism involving specific receptors, a guanine-nucleotide-binding protein and the cyclic AMP-generating enzyme adenylate cyclase.

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