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Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified member of the renin-angiotensin system, is associated with renal organ damage. However, there is little information regarding the regulation of (P)RR expression in various pathophysiological conditions. We therefore examined the expression of (P)RR in the remnant kidneys of rats with renal mass ablation due to 5/6 nephrectomy by quantitative RT-PCR, Western blot analysis and immunohistochemistry. Expression levels of (P)RR mRNA were significantly increased in the remnant kidneys at day 56 after nephrectomy, when compared with sham operation (about 1.6-fold, P=0.001). Western blot analysis showed that expression levels of (P)RR protein were greatly increased in the remnant kidneys at day 56, compared with sham operation (about 7.9-fold, P=0.02). The renal tubular cells were immunostained with anti-(P)RR antibody in both 5/6 nephrectomized rats and sham operated rats. The glomeruli were sporadically immunostained in 5/6 nephrectomized rats, but not in sham operated rats. These findings indicate that the intra-renal (P)RR expression is increased in the remnant kidneys of 5/6 nephrectomized rats, and suggest that (P)RR may contribute to the renal injury.

Adrenomedullin (AM) is a multifunctional regulatory peptide that is produced and secreted by various types of cells. We showed the presence of high concentrations of adrenomedullin-immunoreactivity in the vitreous fluid, and the levels were elevated in patients with proliferative vitreoretinopathy. Furthermore, adrenomedullin mRNA expression levels were elevated in the tissues of intraocular tumors and orbital tumors. Adrenomedullin is produced and secreted by cultured human retinal pigment epithelial (RPE) cells. Inflammatory cytokines and hypoxia are strong stimulators for the adrenomedullin expression in retinal pigment epithelial cells. Adrenomedullin stimulated the proliferation of retinal pigment epithelial cells both under normoxia and hypoxia. Dexamethasone (DEX) increased the adrenomedullin expression in two cultured cell lines of human retinal pigment epithelial cells; ARPE-19 cells and D407 cells, while it had no noticeable effects on the cytokine-induced adrenomedullin expression. These findings suggest that adrenomedullin is involved in the pathophysiology of inflammatory and neoplastic eye diseases as an autocrine or paracrine growth stimulator. The findings on glucocorticoid-induced AM expression raise the possibility that it may be related to the pathogenesis of some eye diseases, such as central serous chorioretinopathy and multifocal posterior pigment epitheliopathy, which are frequently seen in patients treated with high doses of glucocorticoids.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel hypothalamic peptide consisting of 38 amino acids (PACAP1-38) with a potent stimulatory action on adenylate-cyclase in rat pituitary. The presence of PACAP-like immunoreactivity in human brain was studied by radioimmunoassay. Co-localization of PACAP with arginine vasopressin and oxytocin was investigated by immunocytochemistry in the human hypothalamus. Immunoreactive PACAP was detected in all regions of human brain (cortex, thalamus, hypothalamus, pons and hemisphere of cerebellum) with the highest levels found in the hypothalamus (8.5 +/- 1.9 pmol/g wet weight, n = 4, mean +/- S.E.M.). High performance liquid chromatography of the human hypothalamic extract showed that approximately 50% of the immunoreactive PACAP was eluted in the position of PACAP1-38. Immunocytochemical studies showed the presence of PACAP immunoreactive neurons in the paraventricular and supraoptic nuclei of human hypothalamus. PACAP co-localized with arginine vasopressin in magnocellular cells of these nuclei. These findings suggest that PACAP1-38 plays important physiological roles in the human hypothalamus.