VANILLOID RECEPTORS IN THE URINARY-BLADDER - REGIONAL DISTRIBUTION, LOCALIZATION ON SENSORY NERVES, AND SPECIES-RELATED DIFFERENCES

被引:29
作者
SZALLASI, A [1 ]
CONTE, B [1 ]
GOSO, C [1 ]
BLUMBERG, PM [1 ]
MANZINI, S [1 ]
机构
[1] NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA
关键词
VANILLOID RECEPTOR; H-3]RESINIFERATOXIN BINDING; CAPSAICIN-SENSITIVE INNERVATION OF THE URINARY BLADDER; SPECIES-RELATED DIFFERENCES;
D O I
10.1007/BF00166945
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Using selective surgical ablations we have investigated the localization of vanilloid receptors (specific [H-3]resiniferatoxin binding sites) on terminals of the pelvic, hypogastric, and pudendal nerves in the rat urinary bladder. Pelvic and hypogastric nerve resections resulted in 90% and 25% loss of specific [H-3]resiniferatoxin (RTX) binding sites, respectively, whilst pudendic nerve resection had no measurable effect on the binding. In control animals, the density of vanilloid receptors was 1.7-fold higher in the neck than in the dome of the urinary bladder; the B(max) values were 57 +/- 8 and 34 +/- 7 fmol/mg protein, respectively. The binding characteristics of the vanilloid receptor were similar in the urinary bladder of the rat and mouse: K(d) values were 87 +/- 15 and 61 +/- 11 pM, B(max) values were 37 +/- 2 and 60 +/- 10 fmol/mg protein, respectively. In contrast to the findings for the rat and mouse, in the urinary bladder of the guinea pig and the hamster the low level of specific [H-3]RTX binding prevented the detailed characterization of vanilloid receptors. Nonetheless, at a fixed (60 pM) concentration of [H-3]RTX, specific binding both in the guinea pig and hamster urinary bladder was approximately 20% of that in the rat urinary bladder. In the urinary bladder of newborn rats, as in adults, a single class of specific [H-3]RTX binding sites was found which bound RTX with an affinity of 110 +/- 20 pM and with a maximal binding capacity of 30 +/- 5 fmol/mg protein. We conclude that, in accord with the physiological findings, the majority of vanilloid receptors are located on terminals of the pelvic nerve in the rat urinary bladder with higher receptor density in the bladder neck as compared to the bladder dome. Whereas the comparably high density of vanilloid receptors in the rat and mouse urinary bladder and the low receptor density in the hamster are mirrored by the in vivo vanilloid-sensitivity of these species, the low level of vanilloid receptors in the urinary bladder of the guinea pig contrasts to the marked sensitivity of this species to capsaicin. We conclude that the level of vanilloid receptors is an important but not exclusive determinant of vanilloid-sensitivity.
引用
收藏
页码:624 / 629
页数:6
相关论文
共 37 条