Developmental changes in the biochemical and functional properties of endothelin receptors in rabbit renal pelvis.

Abstract

To examine the effect of age on the biochemical and functional properties, and regional distribution of endothelin (ET) receptors in the rabbit renal pelvis. The properties of ET receptors in 6-week-old and 6-month-old male rabbit renal pelves were examined using isolated muscle-bath and radioligand receptor-binding techniques. ET-1 caused a significant increase in the contractile force in muscle strips from all regions of the renal pelvis from both age groups, with the following rank order: upper=middle>lower. The magnitude of the ET-1-induced contractile responses were similar in the lower pelvic regions in both ages, but the responses in the upper and middle regions were significantly greater in younger rabbits. ET-1 increased the frequency of spontaneous activity in a concentration-dependent manner in the upper and middle pelvic regions in both age groups, with significantly smaller ED50 values in the younger than in the older rabbits. In both age groups the lower pelvic region lacked spontaneous activity. The density of total ET receptors was higher in the upper and middle regions of the renal pelvis than in the lower renal pelvis of both ages, with the density in the upper and middle regions being greater in older than in younger rabbits. In all regions, ET subtype selective compounds inhibited [125I]ET-1, binding consistent with the predominance of the ETA receptor subtype, except in the lower region of the older rabbits, in which the densities of ETA and ETB subtypes were similar. In all regions, the younger renal pelvis contained a higher proportion of ETA receptors than in older tissues. Light microscopic autoradiographic data indicated the presence of ETA and ETB receptors in smooth muscle and epithelial cells, respectively. These data indicate the presence of regional differences in the density of ET receptors and in the contractile responses to ET-1 in rabbit renal pelvis, and that although older rabbit renal pelvis contains more total ET receptors than younger renal pelvis, the latter had a higher portion of the ETA receptor subtype and the younger tissues were more responsive to ET-1.