2009 Abstracts - Association for Chemoreception Sciences

supra-threshold discrimination, and peri-threshold intensitydiscrimination performance are obtained. Visual acuity isadditionally measured to verify successful stimulation of V1.Though a limited number of participants have been tested to date,initial analyses indicate that rTMS stimulation of V1 primarilymodulates supra-threshold discrimination and peri-thresholdintensity discrimination performance and has less impact onolfactory identification performance. These initial results indicatethat the primary visual cortex is capable of modulating higherorderolfactory processing.#P138 Poster session III: Cortical chemosensory processing/Receptor genomics and molecular biologyTAS1R1-intronic SNP Associations with Liking for DietarySources of Glutamate and for Orosensory IntensityShristi Rawal 1 , Margaret R. Wallace 2 , John E. Hayes 3 ,Linda M. Bartoshuk 4 , Taimour Y. Langaee 5 , Andrew Sholudko 1 ,Valerie B. Duffy 11Allied Health Sciences, Univ of CT Storrs, CT, USA, 2 MolecularGenetics & Microbiology, Univ of FL Gainesville, FL, USA,3Ctr Alcohol & Addiction, Brown Univ Providence, RI, USA,4Dentistry, Univ of FL Gainesville, FL, USA, 5 CtrPharmacogenomics, Univ of FL Gainseville, FL, USABackground: Gene products of the TAS1R family formheterodimeric receptors that appear to mediate umami(hT1R1+hT1R3) and sweet (hT1R2+hT1R3) sensations (Li et al,2002). Limited information exists on the contribution of TAS1R1variation to functional differences in taste perception, althoughexonic variation has been described in vivo (Kim et al, 2006).Methods: DNA samples from 90 healthy adults were collectedfrom whole bloods, isolated and genotyped for TAS1R1 intronicSNP (rs17492553) by TaqMan genotyping. Results: Similargenotype frequencies were seen in our sample (33% CChomozygous for major allele, 41% were heterozygous, 26%TT homozygous for minor allele) to reference frequencies forEuropean-Americans (50%, 21%, and 29%, respectively). Usingthe sensory and hedonic forms of the general Labeled MagnitudeScale, subjects rated the intensity of: liking and taste quality ofsampled foods/beverages, prototypical tastants painted onfungiform and circumvallate papilla and tasted with the wholemouth; and 25% ethanol painted on the tongue tip. In analysis ofcovariance controlling for age, sex and intensity of tones as across-modal standard, CC adults reported greater liking forsampled soy sauce and white grapefruit juice (sources ofglutamate) than did TT adults, with concurrent increases insourness ratings for the juice. As expected, this SNP failed toexplain differences in liking and sweetness of sampled sweetfoods. However, this SNP explained intensity differences in thespatially-applied ethanol probe and tastants. The TT adults and, insome cases heterozygous adults, reported lower intensities thandid the CC adults. Conclusions: These results support a role ofTAS1R1 SNPs in response to glutamate and further suggest theircontribution to general variability in orosensory intensity.#P139 Poster session III: Cortical chemosensory processing/Receptor genomics and molecular biologyKey amino acid residues involved in multi-point bindinginteractions of sweet protein, brazzein, with the T1R2-T1R3human sweet receptorFariba Assadi-Porter 1 , Emeline L Maillet 2 , James Radek 1 ,John L Markley 1 , Marianna Max 21University of Wisconsin Madison, WI, USA, 2 Mount SinaiSchool of Medicine New York, NY, USABrazzein protein tastes sweet to humans through activation of thesweet sensing receptor heterodimeric GPCR composed ofmonomers T1R2 and T1R3. Brazzein’s sweetness depends onboth its three-dimensional structure and on distributed sites in itssurface chemistry as we have shown by structural, dynamic andfunctional assays (both human psychophysical taste assays andfunctional heterologous expression assays) of wildtype andmutant brazzein proteins. Here we show data from ourinvestigation of three “sweetness” sites on brazzein: loop 43 (Site1); the N and C termini and the proximal Glu36 residue (Site 2);and loop 9-19 (Site 3). We have found that the presence of basicresidues in Site 1, and acidic residues in Site 2 play significant rolesfor brazzein’s sweet taste. We also find that position 54 (Site 2)requires a bulky side chain rather than one with hydrogenbonding potential for sweetness. We determined that properdisulfide bond formation in loop 9-19 (Site 3) is essential forsweetness. We also investigated several areas of the sweet receptorthat modify the brazzein response. We confirmed the involvementof the CRD of T1R3 in brazzein activity by identifying an acidicresidue that is essential for brazzein activity. We alsodemonstrated that the T1R2 VFTM participates in the ability ofbrazzein to activate the sweet receptor, suggesting that it tooforms a point of interaction for brazzein. We have assessed severalmodels for the brazzein binding site within the extracellulardomains of T1R2/T1R3 receptor by mutating charged and polarresidues within the small-molecule binding clefts as well asproximal residues in the interface between and along the backs ofthe T1R2 and T1R3 monomers and characterizing the resultingmutant receptors by a functional calcium mobilization assay.#P140 Poster session III: Cortical chemosensory processing/Receptor genomics and molecular biologyOrbitofrontal lesions and hypersensitivity to olfactory stimuliJulie A. Boyle, Marilyn Jones-GotmanMontreal Neurological Institute, McGill University Montreal,QC, CanadaHypersensitivity to odors has previously been reported in patientswith adrenal cortical insufficiency (Henkin and Bartter, 1966).However, little is known regarding other clinical causes ofhypersensitivity. We studied the olfactory profile two neurologicalpatients complaining of increased sensitivity to olfactory stimuli.Patient 1, MP, is a 40 year old right handed man with multiplecerebral contusions in the frontal, including the bilateralorbitofrontal (OFC) and left temporal (TL) cortices. Detectionthresholds for phenyl ethyl alcohol (PEA) were assessedmonorhinally using an ascending staircase method. MP was ableto detect our weakest dilution of PEA (i.e. 16 th dilution step) ineach nostril. He has tested significantly above his neurologicallynormal peers whose mean sensitivity for PEA has been reportedto range between the 6 th to the 7 th dilution (Deems and Doty,70 | AChemS Abstracts 2009