|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1997 : ¥2,600,000 (Direct Cost : ¥2,600,000)
We investigated the distribution of endothelin (ET) receptors and their functions by using our imazing Analyzer system, including quantitative receptor autoradiography, in situ hybridization and Immunohistochemistry. The obtained results were following.
(1) The pattern of ET_A and ET_B ligand binding sites (ftinctional receptor proteins) in the rat brain was classified to 3 fields ; 1) co-localization of both receptors in the circumventricular organs, and anterior and posterior lobes of the pituitary gland, etc., 2) only ET_A receptor in the Rathke pouch of pituitary gland, etc., 3) only ET_B receptor in the external plexiform layer of olfactory bulb and the Purkinje cell layer.
(2) ET_A receptor proteins were observed in the area posterior, the caudal solitary tract nucleus and dorsal nucleus of the vagus in rat brainstem, whereas ET_A mRNA was localized to only area posterior. Therefore, the presence of ET_A neurons projected to the caudal solitary tract nucleus and dorsal nucleus of the vagus from the area posterior may be considered in rat brainstem. On the other hand, the distribution of ET_B receptor proteins was similar to that of ET_B mRNA, and the ET_B receptors were expressed in the glia cells.
(3) The ET_B receptor was capable of binding ET-1 when ET_A receptor was being occupied by BQ-123, ET_A antagonist. Therefore, A collaboration mechanism between the ET_A and the ET_B receptorS may function in the recognition of ET-1, a typical "bivalent" ligand.
(4) The ET_B receptor was expressed in astrocytes, and the possibility the astrocytes can be activated by ET_B receptor in response to neural tissue repair after neuronal death would have to be considered.
(5) The rat peritoneal macrophages apparently express the ET_B receptor but not the ET_A receptor.