N-geranyl cyclopropyl-carboximide modulates salty and umami taste in humans and animal models

Abstract

Effects of N-geranyl cyclopropyl-carboxamide (NGCC) and four structurally related compounds (N-cyclopropyl E2,Z6-nonadienamide, N-geranyl isobutanamide, N-geranyl 2-methylbutanamide, and allyl N-geranyl carbamate) were evaluated on the chorda tympani (CT) nerve response to NaCl and monosodium glutamate (MSG) in rats and wild-type (WT) and TRPV1 knockout (KO) mice and on human salty and umami taste intensity. NGCC enhanced the rat CT response to 100 mM NaCl + 5 μM benzamil (Bz; an epithelial Na(+) channel blocker) between 1 and 2.5 μM and inhibited it above 5 μM. N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791, a TRPV1t blocker) inhibited the NaCl+Bz CT response in the absence and presence of NGCC. Unlike the WT mice, no NaCl+Bz CT response was observed in TRPV1 KO mice in the absence or presence of NGCC. NGCC enhanced human salt taste intensity of fish soup stock containing 60 mM NaCl at 5 and 10 μM and decreased it at 25 μM. Rat CT responses to NaCl+Bz and human salt sensory perception were not affected by the above four structurally related compounds. Above 10 μM, NGCC increased the CT response to MSG+Bz+SB-366791 and maximally enhanced the response between 40 and 60 μM. Increasing taste cell Ca(2+) inhibited the NGCC-induced increase but not the inosine monophosphate-induced increase in glutamate response. Addition of 45 μM NGCC to chicken broth containing 60 mM sodium enhanced the human umami taste intensity. Thus, depending upon its concentration, NGCC modulates salt taste by interacting with the putative TRPV1t-dependent salt taste receptor and umami taste by interacting with a Ca(2+)-dependent transduction pathway.