Olfaction by melanophores: what does it mean?

Abstract

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...

Cell cultures of neuroblasts from rat olfactory epithelium that show odorant responses.

“…This may be similar to the desensitization described for other receptormediated adenylyl cyclase systems such as catecholamines and glucagon (27). (28) to suggest that separate physiological responses may be involved. Perhaps, when these phenomena can be studied more completely in cloned cell strains, it will turn out that the millimolar responses are less discriminating and less likely to involve the reactions that confer specificity in olfaction than are the submicromolar responses.…”

Selective imaging of presynaptic activity in the mouse olfactory bulb shows concentration and structure dependence of odor responses in identified glomeruli

“…A weak and spatially nearly homogenous activation level was observed exclusively at high concentrations. It is clearly distinguishable from the main signal, has the hallmarks of an unspecific interaction, and might be caused by the chemical reactivity of aldehydes and͞or non-receptor-mediated activation of ORN (31). Thus, the olfactory representation or code at the level of the OR is sparse at low concentrations but dense at high concentrations.…”

Some sweet and bitter tastants stimulate inhibitory pathway of adenylyl cyclase via melatonin and α2-adrenergic receptors in Xenopus laevis melanophores

“…Therefore, these results call for an examination of the similarity between the melatonin receptors and those of newly identified sweet and bitter GPCRs (4,7,20,21,27). Interestingly, some odorants have been shown to induce pigment dispersion and AC activation in X. laevis melanophores (17). These results were interpreted as nonreceptor activa- tion of AC.…”

“…In addition, some amphipathic (possessing both hydrophobic and hydrophilic domains) bitter tastants and nonsugar sweeteners can rapidly permeate taste cells against a concentration gradient (29) and, like other amphipathic compounds (22,37), can activate G proteins directly in vitro (26). Furthermore, some odorants were shown to induce pigment dispersion and activation of adenylyl cyclase (AC) pathway (increase in cAMP content) in Xenopus laevis melanophores, which are nonolfactory by nature, suggesting nonspecific effects by such odorants (17). These results led to the hypothesis that amphipathic tastants stimulate transduction pathways by means of receptor-dependent and receptor-independent mechanisms, as proposed for other systems (1,6), which in the taste system may be related to the delayed temporal properties (e.g., lingering aftertaste) induced by such tastants (24).…”