[Histocytochemical and functional aspects on the "brain-vascular peptides"]

The vasoactive peptides, endothelins (ET-1, ET-2 and ET-3: ETs), natriuretic peptide family (ANP, BNP and CNP:NPs) and angiotensins (I, II, III and IV), exist in not only cardiovascular organs but also in the central nervous system. In the central nervous system, these peptides play important roles to maintain the water balance, electrolyte metabolism and blood pressure control as neural messengers. For this reason, we proposed that these peptides are "brain-vascular peptides" after the model of the "brain-gut peptides." Recent reports showed that these peptides also have the other common character to play significant roles for cell differentiation and/or proliferation or morphogenesis in various peripheral organs as cytokine/growth factors. We have consecutively studied the endogenous digitalis-like substance (sodium transport inhibitor), NPs and ETs by histocytochemical analysis. This article reviews (1) newly developed histological procedure for analyzing the biochemical and functional basis of brain-vascular peptides, e.g., a new technique for raising polyclonal antibody to distinguish their molecular form; c-fos expression analysis; TUNEL staining; culture-in-oculo-chamber; and preparation of transgenic mice; (2) the synthesis and secretion of endothelins, their distributions, target sites, signal transduction and physiological actions; (3) histocytochemical studies on ETs, NPs and angiotensins in the central nervous system as the neural messengers; (4) histocytochemical and pharmacophysiological studies on ETs, NPs and angiotensins as the cytokine/growth factors.