strychnine and sucrose-octaacetate

Inbred and congenic strains exhibited several patterns of relative sensitivity to bitter tastants in 48-h, two-bottle preference tests. With segregation analyses of descendents of crosses between contrasting strains, these patterns suggested at least three genetic loci influencing bitter perception. The extensively characterized Soa (sucrose octaacetate) locus underlies one pattern. Variation at this locus had pleiotropic effects on avoidance of other acetylated sugars, plus such structurally dissimilar bitter tastants as brucine, denatonium benzoate, and quinine sulfate. Unlike SOA, however, sensitivity to quinine sulfate was polygenically determined, and produced a second characteristic pattern. At least one, possibly several, additional unlinked loci contributed to quinine differences. Phenylthiocarbamide (PTC) aversion differences exemplified a third pattern. Segregation consistent with monogenic control of PTC aversion has been reported, and within segregating populations PTC aversion did not covary with SOA or quinine sulfate avoidance. Variants of the three major patterns may be useful for analysis of specific mechanisms. While both showed the SOA pattern, strychnine differences were markedly smaller than brucine (dimethoxystrychnine) differences. Likewise, a hop extract containing primarily iso-alpha acids (e.g., isohumulone) produced an SOA-like pattern, while an extract with nonisomerized alpha-acids (e.g., humulone) did not.

Topics: Animals; Chromosome Mapping; Cyclohexenes; Cyclopentanes; Dose-Response Relationship, Drug; Female; Food Preferences; Male; Mice; Mice, Inbred Strains; Phenotype; Phenylthiourea; Quaternary Ammonium Compounds; Species Specificity; Strychnine; Sucrose; Synaptic Transmission; Taste; Taste Buds; Taste Threshold; Terpenes

It is probable that there is a diversity of mechanisms involved in the transduction of bitter taste. One of these mechanisms uses the second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Partial membrane preparations from circumvallate and foliate taste regions of mice tongues responded to the addition of known bitter taste stimuli by increasing the amount of inositol phosphates produced after 30 s incubation. Addition of both the bitter stimulus, sucrose octaacetate and the G-protein stimulant, GTP gamma S, led to an enhanced production of inositol phosphates compared with either alone. Pretreatment of the tissue samples with pertussis toxin eliminated all response to sucrose octaacetate plus GTP gamma S, whereas pretreatment with cholera toxin was without effect. Western blots of solubilized tissue from circumvallate and foliate regions probed with antibodies to the alpha-subunit of several types of G-proteins revealed bands reactive to antibodies against G alpha i1-2 and G alpha o, with no apparent activity to antibodies against G alpha i3. Given the results from the immunoblots and those of the toxin experiments, it is proposed that the transduction of the bitter taste of sucrose octaacetate in mice involves a receptor-mediated activation of a Gi-type protein which activates a phospholipase C to produce the two second messengers, IP3 and DAG.

Topics: Animals; Caffeine; Female; GTP-Binding Proteins; Inositol Phosphates; Male; Membrane Potentials; Mice; Mice, Inbred Strains; Quaternary Ammonium Compounds; Second Messenger Systems; Signal Transduction; Strychnine; Sucrose; Synaptic Transmission; Taste; Taste Threshold; Type C Phospholipases