Am. J. Respir. Crit. Care Med., Vol 152, No. 1, Jul 1995, 59-63.
Resiniferatoxin binding to vanilloid receptors in guinea pig and human airways
A Szallasi, C Goso and S Manzini
Department of Physiology and Pharmacology, Karolinska Institute, Sweden.
We have used the [3H]resiniferatoxin (RTX) binding assay to characterize
for the first time a vanilloid (capsaicin) receptor in tracheobronchial
tissues of the guinea pig. Membranes obtained from the trachea and the main
bronchi bound RTX with an affinity of 1 nM; the cooperativity index was
close to unity, indicating noncooperative binding. Specific [3H]RTX binding
was fully inhibited by capsaicin (Ki = 500 nM) and capsazepine (Ki = 100
nM), but it was not inhibited at all by the inactive RTX structural analog
resiniferonol 9, 13, 14- orthophenylacetate (10 microM), confirming the
specificity of the binding. Neither was RTX binding inhibited by the
functional vanilloid antagonist ruthenium red (100 microM). The density of
specific RTX binding sites was similar in the trachea (Bmax = 150 fmol/mg
protein) and the bronchi (Bmax = 170 fmol/mg protein). In keeping with the
marked resistance of hamsters to capsaicin actions, no specific RTX binding
could be detected in the airways of this species. By contrast, we have been
able to demonstrate specific RTX binding sites in human bronchi: the
estimated affinity for RTX, 2 nM, was similar to that (7 nM) determined in
guinea pig bronchi. We conclude that (1) the [3H]RTX binding assay affords
a novel biochemical marker for vanilloid- sensitive nerves in the airways,
and (2) this binding assay may be a useful tool to explore species-related
differences in the expression and pharmacologic profile of vanilloid
receptors in the airways.
