Hypotheses on general olfaction can be divided into two broad groups: those that predict the existence of olfactory-specific olfactory receptor proteins and those that do not. Recently, much attention has been paid to the discovery of an odorant-stimulated adenylate cyclase in purified olfactory cilia. This finding has, for the most part, been accepted as evidence that the former hypotheses are correct. Here we report that frog melanophores, which are nonolfactory in nature, disperse their melanosomes in response to the same types and concentrations of odorants used in the investigations ofolfactory cilia and that pigment dispersion is accompanied by rises in intracellular cAMP levels. The effects show that the existence of a cAMP-based second messenger system in olfactory cilia is not in itself proof of the existence of olfactoryspecific olfactory receptor proteins. Also they explain the basis of Ottoson's pioneering work of 30 years ago on the electrical responses of frog olfactory epithelium to stimulation with alcohols. The results suggest that there could be two mechanisms that are important for the detection of odorants: one based on specific receptors, the other nonspecific, but both working through activation of cAMP.Many cellular processes are mediated by cAMP and recently olfaction has been added to this list (1-3). The sense of smell in vertebrates is a property of the olfactory neuroepithelium. While this epithelium contains several types of cells that are important for olfaction, the bipolar receptor neurons are ultimately responsible for odorant detection. These neurons are physically striking for the tuft of cilia sprouting from the bulbous expansion that marks the end of each dendrite (4). The cilia, which in some animals exceed 100 ,uM in length, form an interlacing meshwork intercalated into mucus covering the epithelium. Because of their physical location the olfactory cilia have long been thought to be the primary detectors of odorants. In support of this premise cilia have now been shown to contain high levels of the GTP binding protein Gs, a cAMP-gated conductance, and an adenylate cyclase that can be activated by incubation of the cilia with odorants applied at concentrations in the range of 100 to 250 ,uM (1)(2)(3)5). However, the molecular nature of olfactory receptors themselves has remained obscure.Many proteins have been suggested as candidates for being olfactory receptors (6-9). That no specific receptor proteins may be required for general olfaction has also been suggested (10-12). We decided to determine whether odorants could activate adenylate cyclase in cells that were neither neuronal nor olfactory in nature. Melanophores were chosen because activation of adenylate cyclase results in a rapid and easily observable change in phenotype.Melanophores, which are found in many vertebrates, contain organelles called melanosomes that are filled with the dark brown pigment melanin. The melanosomes can be moved either centripetally or centrifugally within the cells in response to...

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