Specific binding of [ 3H]resiniferatoxin by human and rat preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus membrane preparations

• Published in: Life sciences (1973) 1996-10, Vol.59 (22), p.1899-1908
• Main Authors: Acs, Geza, Palkovits, Miklos, Blumberg, Peter M.
• Format: Article
• Language: English
• Subjects: 3H]RTX binding; Animals; Binding Sites; Brain - metabolism; capsaicin; Capsaicin - pharmacology; Diterpenes - metabolism; Female; Humans; locus ceruleus; medial hypothalamus; preoptic area; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Drug - drug effects; Receptors, Drug - metabolism; reticular formation and ventral thalamus; Tritium; vanilloid receptors
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(96)00537-1

Specific [ 3H]resiniferatoxin (RTX) binding detects the vanilloid (capsaicin) receptors and provides a biochemical means for exploring their pharmacology. In the present study we demonstrate specific vanilloid (RTX) binding sites in various brain areas not known to be innervated by primary afferent neurons. Specific high-affinity binding of [ 3H]RTX could be detected in membrane preparations of the posterior (“hypothalamic”) and anterior (“septal”) parts of the preoptic area, locus ceruleus, medial hypothalamus, brainstem reticular formation and ventral thalamic nuclei from naive rats. The determined levels of binding at 4 nM [ 3H]RTX were 23.0 ± 4.5, 7.1 ± 1.6, 29.9 ± 2.3, 23.5 ± 2.4, 9.9 ± 2.2 and 8.1 ± 1.9 f mol mg , respectively; unfortunately, the high levels of non-specific binding (higher than 80%) in the present experiments made it impossible for us to characterize fully the binding properties of the receptors. However, no detectable specific [ 3H]RTX binding was present in membranes of brain nuclei from rats pretreated with 300 mg kg capsaicin, a treatment which causes loss of response to capsaicin. Significant specific [ 3H]RTX binding was also absent in membrane preparations of the midbrain central gray matter, somatosensory cortex and cerebellum either from naive or capsaicin treated rats. In human brain specific [ 3H]RTX binding measured at 4 nM [ 3H]RTX showed a pattern of distribution similar to that in the rat brain. The corresponding levels of specific [ 3H]RTX binding in the preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus were 44.9 ± 2.4, 50.6 ± 3.0, 36.1 ± 2.9, 9.4 ± 2.8 and 8.4 ± 2.4 f mol mg , respectively. Our findings corroborate previous biological evidence that vanilloid receptors are present in brain as well as in sensory afferent neurons.