Gustatory Chemoreception in Man: Multi-disciplinary Aspects and Perspectives

GUSTATORY CHEMORECEPTION IN MAN: MULTIDISCIPLINARY ASPECTS AND PERSPECTIVES ROLAND FISCHER, FRANCES GRIFFIN, and MARSHA A. ROCKEY* The aim of this paper is to review certain multidisciplinary aspects of research on human tasteperformed in our laboratory, to relate our data to other ongoing research, and to discuss problems and trends that necessarily result from such an integration. Our particular slant has been to look at the human oral cavity as a pharmacological preparation in situ. We came to regard the gustatory response as a sensory expression of chemoreception, a feedback loop reflecting systemic (re)activity. Receptor Concepts Aspects ofdrug-receptor interaction may serve as the stage ofthe search for models of gustatory chemoreception. The by-now-classic idea of a receptor as a structure that binds drugs originated in 1913 with Ehrlich [1]: "Corpora nonagunt nisi fixata." In Schueler's [2] more specific words, the drug receptor is, in general, a pattern of forces of diverse origin forming a part of some biological system and having roughly the same dimensions as the pattern of forces presented by the drug molecule such that between the two patterns a relationship of complementarity for interaction exists. This interaction may originate in sites of strongly reduced electron density, a common characteristic in the molecular architecture ofbiologically active drugs [3]. We may derive the simplest model of a receptor from the work of Beckett and Anderson [4]. They prepared "footprints" in silica gel by forming the gel in the presence ofa reference molecule. Specifically, when * Division of Behavioral Sciences, Department of Psychiatry, College ofMedicine, Ohio State University, Columbus, Ohio 43210. These studies were supported in part by U.S. Public Health Service National Institutes of Health grants M-2731, M-4694, 42071, MH-07479 and by General Research Support grants administered through the College of Medicine, Ohio State University. This paper is gratefully dedicated to Chauncey D. Leake, master scholar and friend. 549 silica gel is prepared in the presence ofquinine and then extracted until no more alkaloid is releasedfrom the powder, anadsorbent results, the surface ofwhich appears to contain molecular imprints of the desired configuration . This adsorbent can distinguish between the configuration of stereoisomers ofstructure not too dissimilar from that ofquinine; for example, cinchonidine (configurationally related to quinine) is adsorbed more readily by the adsorbent than its stereoisomer, cinchonine (configurationally related to quinidine). It is believed that the "footprinted" molecules become trapped in the gel. The free hydroxyl groups in the surface ofthe gel apparently interact with the electrons of aromatic nuclei and basic centers. Molecules of the correct geometry and surface characteristics are strongly attracted to the "active-site" footprints [5], which represent an informational matrix. A more complex receptor model, already in possession of structured information, is the fibrous protein, wool. Wool or hair keratin is an extensible , coherent, water-insoluble protein with disulphide-linked polypeptide chains, the specific configuration of which is based on the a-helix [6, 7]. From an aqueous solution ofthe racemates ofmandelic acid, wool will selectively adsorb (+)-mandelic acid [8]. It is believed that the resolution ofmandelic acid on wool occurs at its "active site," at the L-arginine and L-lysine residues, mainly in the crystalline region ofthe fiber [9]. An extensive review ofthe resolution ofracemates by asymmetric adsorption is available in Klabunovskii [10]. The first of Clark's [11] quantitative concepts holds that the maximal response requires complete occupation of receptors by the drug. Curves depicting a relation between concentration and action are hyperbolic and, with increasing concentration, asymptotically approximate a maximum. The Langmuir adsorption equilibrium, the Weber-Fechner law, and the dissociation curve for oxyhemoglobin in hemoglobin as a function of O2 tension are such representative functions. Clark assumed a positive correlation between the measured intensity ofbiological activity and the percentage of occupied receptor molecules, implying that maximum effect can occur only when complete occupation ofreceptors is achieved by drug molecules. Clark's model implies that the activity of a drug depends on its affinity for the receptor. Our work, which quantitatively measured the affinity of chemicals to wool protein and related affinity to biological activity, regarded the wool 550 Roland Fischer et al. · Gustatory Chemoreception in Man Perspectives in Biology and Medicine · Summer 1966...