The Bidirectional Modulatory Effects of Ribonucleotides on Glutamate Detection Thresholds

Abstract

Abstract Objectives The objective of this study was to determine the effect of 5’-ribonucleotides on the absolute detection threshold of L-glutamate. We hypothesized that the addition of these and other ribonucleotides would decrease the absolute detection threshold of L-glutamic acid potassium salt (MPG) when in admixture; thus, sensitivity to glutamate would be increased in their presence. Methods The absolute detection thresholds of MPG were measured in 17 healthy volunteers and compared to the detection threshold for MPG in the presence of a background level of 5’ ribonucleotide guanosine-, inosine-, adenosine-, uridine-, or cytosine-monophosphate disodium salt (3 mM). Results The average detection threshold of MPG was 1.90 × 10−03 M. We found the additions of inosine 5'-monophosphate (IMP), guanosine 5'-monophosphate (GMP), and adenosine 5'-monophosphate (AMP), lowered the MPG detection threshold for every subject and were statistically significant (p < 0.001), suggesting they are positive modulators of glutamate taste. IMP was the most robust enhancer of MPG detection and decreased the detection threshold by a factor of 41.4 to a concentration 4.60 × 10−05 M. GMP and AMP decreased the detection threshold of glutamate by a factor of 27.3 and 8.2, respectively. UMP and CMP, however, yielded different results. Interestingly, CMP raised glutamate detection thresholds in 60% of subjects, suggesting it is an inhibitor or negative modulator of glutamate taste in humans. The addition of UMP to the MPG solution produced mixed results and did not significantly modulate the detection of MPG. The rank order of effects on increasing sensitivity to glutamate was IMP > GMP > AMP, whereas CMP appeared to decrease sensitivity to glutamate. Conclusions Ribonucleotides are modulators of the detection threshold of glutamate.Some, such as IMP, are enhancers of glutamate taste, and others, such as CMP, appear to be suppressors of glutamate taste. This may be due to positive and negative allosteric modulation, respectively, of the T1R1/T1R3 glutamate receptor in the oral cavity. Funding Sources P.A.S.B. was funded by by NIH NIDCD RO1 014286 as Co-PI and NJ Hatch Project No.NJ14120.