Abstract

We have used the vanilloid (capsaicin) receptor assay to search for modulators of binding activity. We report here that both capsaicin and its ultrapotent analog, resiniferatoxin (RTX), bind to the plasma protein alpha-1-acid glycoprotein (AGP) with high affinity (10.5 and 0.3 microM, respectively). AGP seems to be the dominant vanilloid (capsaicin/RTX) binding protein in serum. [3H] RTX binding to AGP is inhibited by chlorpromazine and by Trisbutoxyethylphosphate, indicating that vanilloids compete for a well-characterized drug binding domain on the AGP molecule. The 35-fold difference in the affinity of AGP for RTX and capsaicin may result in differences in the pharmacodynamics and pharmacokinetics of these two compounds; the contribution of AGP binding to the unique spectra of action of RTX or to the marked species differences in vanilloid actions, however, remains to be determined. An important practical application of AGP is its inclusion in the [3H]RTX binding assay utilizing sensory ganglion membranes to reduce nonspecific binding by up to 5-fold.