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W Jakinovich

Publications and source records attributed to W Jakinovich.

16 recordsLinked to original sources

Single neuron gustatory responses of the gerbil chorda tympani to a variety of stimuli (recorded by a new method).

In most mammalian studies on gustatory single neuron recordings, the animal's chorda tympani nerve was cut and manipulated. This results in nerve trauma which may have affected the precision of the responses. In this paper, we are presenting a method whereby gustatory recordings were obtained from gerbil single chorda tympani neurons by inserting a microelectrode directly into the uncut nerve. The stimuli included 0.3 M NaCl, 0.3 M KCl, 0.3 M CaCl2, 0.3 M NH4Cl, 0.05 M acetic acid, 0.01 M quinine HCl, 32% Polycose and the sweeteners 0.5 M D-glucose, 0.5 M D-fructose, 0.02 M sodium saccharin and 0.5 M sucrose. While thirty-seven of the sixty seven neurons tested did not respond to any of the eleven gustatory stimuli applied to the gerbil's tongue, thirty positive single neuron responses were obtained to this group of compounds. The thirty positive neuron responses were grouped in two ways: (1) by observationally sorting the data according to maximum responses to four stimuli, sucrose, NH4Cl, NaCl, and acetic acid; and (2) by objectively sorting the data matrix using cluster analysis. The groups resulting from each method were then characterized and compared by discriminant function analysis. By the first grouping method, ten neurons responded best to sodium chloride, seven to acetic acid, four to ammonium chloride, and nine to sucrose. However, canonical discriminant function analysis showed that two of the four groups, acetic acid and ammonium chloride, occupied the same region of discriminant space and should be combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Antagonism of the gerbil's sweetener and Polycose gustatory responses by copper chloride.

Antagonism of the gerbil's whole chorda tympani nerve taste responses by CuCl2 was studied. A 30 min pretreatment of 0.1 mM CuCl2 suppressed responses to single concentrations of the following sweeteners: L-alanine, L-proline, D-tryptophan, 6-chloro-D-tryptophan, L-valine, glycine, sucrose, maltose, lactose, tetrachloro-galacto-sucrose, glucose, fructose, methyl alpha-D-glucopyranoside, glycerol, sorbitol, sodium saccharin, L-4'-cyano-3'-(2-2-2-trifluoro acetamido)succinanilic acid, phenethyurea, and stevioside. The responses to L-serine and the starch hydrolysate, Polycose were depressed to a lesser degree. The responses to glycine HCl and NaCl were slightly suppressed by CuCl2. The 0.1 mM CuCl2 had no effect on the shape of the sucrose concentration-response curve or its 1/2 maximal response (CR50), but did suppress the maximum response (Rmax), characteristic of non-competitive antagonism. Our work suggests the presence of 2 separate receptor sites on the gerbil's taste receptor cell membrane, one of which interacts with sugar sweeteners and most other non-sugar sweeteners and the other with Polycose.

Amino Acids↗

Modification of the gerbil's taste behavior by the sucrose taste antagonist p-nitrophenyl alpha-D-glucopyranoside.

Since the gerbil's chorda tympani nerve response to sucrose is antagonized by p-nitrophenyl alpha-D-glucopyransoide (PNP-Glu), the present taste aversion behavioral experiments sought to determine whether the gerbil's behavioral gustatory responses could be modified by adding PNP-Glu to taste solutions. Results demonstrated that the gerbil's aversion to sucrose was affected by the addition of PNP-Glu, but that the avoidance was overcome by the addition of high enough concentrations of the antagonist. When mixtures of sucrose and quinine were tested, the gerbil's sucrose aversion was unaffected, nor was any change noted in the taste behavior of gerbils trained to avoid 0.1 M sodium chloride after the addition of PNP-Glu.

Animals↗

A structure-activity study on the sucrose taste antagonist methyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside.

In order to assess the effect of the antagonist methyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside (MAD-diCl-Gal) upon the gerbil's chorda tympani sucrose taste response, we tested several concentrations of this compound, as well as single concentrations of closely related derivatives, and found that MAD-diCl-Gal was the most potent inhibitor tested. It appears that the inhibition mechanism is very specific. For example, we have found that 2 chlorine atoms at the C-4 and C-6 positions on the glucopyranoside ring are required for inhibition. In addition, with regard to the orientation of the chlorine atoms, the galacto derivative seems to be more potent than the gluco derivative. We have also found that the methyl glycoside is more potent than the free sugar. With regard to the orientation of the methyl group, MAD-diCl-Gal is more potent than its beta-anomer. (Because of this discovery of the methyl group enhancement and orientation effect, we shall discontinue using the acronym diCl-Gal and replace it with the more specific MAD-diCl-Gal.) Of particular significance is the fact that there appears to be a structure-activity relationship between the most active stimulants and inhibitors in that the requirement for an axial orientation at C-1 and the enhancement by the methyl group at that position are the same in both cases. These results suggest that both the stimulator and the antagonist are acting at the same receptor site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antagonism of the gerbil's sucrose taste response by p-nitrophenyl alpha-D-glucopyranoside and chloramphenicol.

We have discovered that the gerbil's chorda tympani nerve response to sucrose is suppressed by p-nitrophenyl alpha-D-glucopyranoside (PNP-Glu) and chloramphenicol (CAP). Mixture experiments of PNP-Glu and CAP with sodium chloride, potassium chloride, hydrochloric acid, and sucrose gave rise to the following observations: Neither PNP-Glu nor CAP alone stimulates the gerbil's taste nerve; while the sucrose response is suppressed by these inhibitors, taste responses produced by sodium chloride, potassium chloride, and hydrochloric acid are unaffected by the presence of PNP-Glu or CAP; the antagonisms of PNP-Glu and CAP were surmounted by a high concentration of sucrose; CAP is a more potent antagonist (IC50 = 0.0013 M) than PNP-Glu (IC50 = 0.022 M), and both are more potent than methyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside (IC50 = 0.048 M); and sucrose antagonism occurs only when PNP-Glu and CAP are mixed with sucrose. It is short-lived and ceases when the mixtures are rinsed from the gerbil's tongue. Structure-activity studies provided the following information: The alpha anomer of PNP-Glu is a more potent inhibitor than its beta anomer; among the PNP-Glu derivatives tested (p-aminophenyl, p-nitrophenyl, and phenyl) only p-nitrophenyl inhibited; among the nitrophenyl galactosides, the para derivative was more potent than the ortho or meta; and p-nitrophenyl alpha-D-mannopyranoside and p-nitrophenyl alpha-D-galactoside are slightly more potent than PNP-Glu. On the basis of concentration experiments, we believe that the inhibitory mechanisms of PNP-Glu and CAP are different, which suggests the existence of at least 2 sucrose receptor sites.

Animals↗

Methyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside: an inhibitor of sweet taste responses in gerbils.

The sugar methyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside (DiCl-gal) is a new type of inhibitor of the gerbil's electrophysiological taste response to sucrose or saccharin. Saturated solutions of this compound alone barely stimulate the gerbil's taste nerve. But, when mixed with sucrose or saccharin, DiCl-gal suppresses the gerbil's taste response to these two sweeteners. In contrast, when mixed with sodium chloride or hydrochloric acid, DiCl-gal does not affect the taste responses to these compounds. However, unlike other inhibitors of sweet taste, the DiCl-gal taste suppression is short-lived and occurs only when the inhibitor is combined with the sweetener.

Action Potentials↗

Taste aversion to sugars by the gerbil.

Some conditioned taste aversion experiments were undertaken to determine how the gerbil responds to disaccharides, monosaccharides and polyols. We observed the following: animals taught an aversion to 0.1 M sucrose generalized the avoidance to most sugars, the exception being galactitol; animals taught to avoid 0.01 M hydrochloric acid generalized the avoidance towards lactose, cellobiose, maltitol, methyl alpha-D-galactopyranoside, methyl alpha-D-mannopyranoside, methyl beta-D-glucopyranoside, and glycerol; animals taught to avoid 0.001 M quinine . HCl generalized the avoidance towards methyl alpha-D-glucopyranoside, methyl-beta-D-glucopyranoside, glycerol, ethylene glycol and erythritol. In no case did animals taught to avoid 0.1 M sodium chloride avoid any of the sugars. Moreover, it was observed that the gerbil's behavior with most reducing sugars was different than with equivalent methyl glycosides. For example, animals that were taught to avoid sucrose generalized the avoidance towards reducing sugars, such as, D-galactose, D-glucose, and D-mannose. However, the methyl glycosides, such as methyl alpha-D-glucopyranoside, methyl beta-D-glucopyranoside, methyl alpha-D-galactopyranoside and methyl alpha-D-mannopyranoside, in addition to being avoided by animals taught to avoid sucrose, were also avoided by animals taught to avoid quinine . HCl or hydrochloric acid. In addition, we have observed that the control animals consumed differing amounts of sugars and have concluded, therefore, that the sugars were not equally pleasant despite our attempt to use concentrations which produced equally intense neural responses in the gerbil's chorda tympani nerve.

Animals↗

Stimulation of the gerbil's gustatory receptors by saccharin.

The gustatory responses from the chorda tympani nerve of the Mongolian gerbil, Meriones unguiculatus, were tested with saccharin and some closely related compounds. Only two compounds, saccharin and 6-chlorosaccharin, stimulated the gerbil's taste receptors to any degree and in the same order in which they are sweet to man, saccharin greater than 5-chlorosaccharin. Those compounds which are tasteless to man did not stimulate and include N-methyl saccharin, phthalimide, and O-sulfobenzoic acid. These nonstimulating derivatives did not inhibit the saccharin electrophysiological response. The saccharin taste response pH optimum is from 5 to 8. At pH 7 and 8, saccharin is fully ionized and is binding to the receptor site by an anionic mechanism. Kinetic plots of the taste response at pH 7 indicate that saccharin is forming 1:1 complexes with it. In addition, mixtures of saccharin and sucrose stimulate in such a manner as to suggest that they are interacting at different receptor sites.

Animals↗

Stimulation of the gerbil's gustatory receptors by artificial sweeteners.

Some electrophysiological and behavioral taste experiments have been undertaken to determine how the Mongolian gerbil responds to artificial sweeteners. In the electrophysiological experiment only fourteen of twenty-one sweeteners produced neural responses. The most potent compound was L-4'-cyano-3-(2,2,2-trifluoroacetamido)succinanilic acid. Halogenated derivatives were more potent stimuli than non-halogenated ones. D-Tryptophan was stimulatory while L-tryptophan was not. The electrophysiological responses to sucrose were not inhibited by the presence of non-stimulating sweeteners nor were the responses to D-tryptophan inhibited by L-tryptophan. All the compounds that were stimulatory electrophysiologically were used in the behavior experiment. Using conditioned taste aversion, the gerbils responded to 5 of the compounds as sweet, one as sweet-salty, two as sweet-bitter, one as sour and one as bitter. In addition, 3 compounds were drunk equally by all groups suggesting that they were tasteless or possessed some unknown taste quality. A correlation was found between the efficacy (Kd) of the sweet-tasting compounds (pure sweet or mixed sweet) and the sweetness ranking by humans.

Animals↗

Zinc nutrition and salt preference in rats.

Zinc-deficient rats have an increased preference for sodium chloride (saltwater). We investigated the possibility that this elevated saltwater preference is due to nonfunctional taste receptors. In experiment I, zinc-deficient rats consumed more saltwater than zinc-sufficient rats at most sodium chloride concentrations tested (0.001-1.0 M). When the zinc-deficient rats were fed a zinc-sufficient diet, the clinical symptoms of zinc deficiency rapidly disappeared. However, the rats still preferred saltwater to a greater extent than rats maintained on the zinc-sufficient diet. In experiment II, rats fed diets supplemented with levels of zinc below the requirement for maximum growth had an increased preference for saltwater (0.15 M NaCl). In experiment III, electrophysiological responses of the taste nerves to various concentrations of sodium chloride, sucrose, quinine . HCl, and hydrochloric acid were the same in both zinc-deficient and zinc-sufficient rats. We conclude that the taste receptor sensitivity of the rat is not impaired by zinc deficiency. The increased salt preference of zinc-deficient rats might be related to some endocrine or central nervous system disorder precipitated by inadequate dietary zinc.

Animal Nutritional Physiological Phenomena↗

Stimulation of the gerbil's gustatory receptors by disaccharides.

The gustatory responses from the chorda tympani nerve of the Mongolian gerbil, Meriones unguiculatus, were treated with 13 disaccharides. Sucrose was the most stimulatory sugar. The ability of fructosyl glycosides to stimulate may depend upon the linkage between fructose and the glycoside. Disaccharides possessing 1 leads to 3, 1 leads to 4, or 1 leads to 6 linkages were poor stimuli compared to sucrose which has a 1 leads to 2 linkage. Glucopyranosyl disaccharides with an alpha-linkage were better stimuli than the beta-anomers, while galactopyranosyl disaccharides possessing a beta-linkage were better than their alpha-amoners.

Animals↗

Stimulation of the gerbil's gustatory receptors by monosaccharides.

The gustatory responses of the Mongolian gerbil were tested with a large number of monosaccharides. Electrophysiological methods were used to record from the chorda tympani nerve. Methyl glycosides which have structural features in common with sucrose are the most effective monosaccharides for eliciting a neural response. Among the monosaccharides tested, efficacy appears to be highest in D-pyranosides having equatorial substituents at the C-2 and C-4 positions and axial substituents at the C-1 position. A C-5 hydroxymethyl group is not required. Similarities in the structural requirements for taste response in the fly and gerbil are discussed.

Animals↗

Stimulation of the gerbil's gustatory receptors by polyols.

The gustatory responses of the Mongolian gerbil were tested with 12 sugar alcohols. The electrophysiological effectiveness of the linear polyols as gustatory stimulants increased as the length of the carbon chain increased from 2 to 5. Six and 7 carbon acyclic polyols were no more effective than the pentitols. By comparison myoinositol, a cyclic polyol, was more effective in evoking a response. Responses to mixtures of D-sorbitol and sucrose suggest that these sugars compete for a common receptor site. A sucrose receptor site and a model of it is proposed.

Animals↗

Evaluation of plant extracts for sweetness using the Mongolian gerbil.

Extracts of Thladiantha grosvenorii fruits, Stevia rebaudiana leaves, and Abrus precatorius leaves were investigated using Mongolian gerbil electrophysiological and conditioned taste aversion procedures, which were designed to respond to sucrose. A close correlation was observed between extracts of these sweet plants known to contain sweet principles and those extracts indicated as being sweet by a combination of these gerbil bioassays. The methods employed seem to be suitable for use in aiding the purification of highly sweet compounds of plant origin.

Animals↗