Expression of (pro)renin receptor in the human brain and pituitary, and co-localisation with arginine vasopressin and oxytocin in the hypothalamus.

(Pro)renin receptor [(P)RR], a specific receptor for renin and prorenin, is a 350 amino acid protein with a single transmembrane domain. In the present study, the expression of (P)RR in the human brain and pituitary, and its co-localisation with arginine vasopressin and oxytocin in the human hypothalamus were studied by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry. Human brain and pituitary tissues were obtained at autopsy from the subjects without neurological or endocrinological disorders. The antiserum against (P)RR was raised in a rabbit by injecting the peptide fragment of human (P)RR corresponding to 224-237 amino acids conjugated with bovine serum albumin. Quantitative RT-PCR showed that (P)RR mRNA was widely expressed in every region of brain examined and pituitary, with the highest expression levels found in the pituitary and frontal lobe. Immunocytochemistry showed that (P)RR was expressed in the paraventricular and supraoptic nuclei of human hypothalami, and in anterior pituitary cells. Immunostaining of serial sections showed that (P)RR was co-localised with arginine vasopressin and oxytocin in the magnocellular neurones of the paraventricular and supraoptic nuclei. The preabsorption of the antibody by the antigen peptide abolished the immunostaining of (P)RR in the human hypothalamus. The present study has shown that (P)RR mRNA is widely expressed in the human brain and pituitary, consistent with the hypothesis that (P)RR is related to the various brain functions, such as cognitive function and brain development. Co-localisation of (P)RR with vasopressin in the hypothalamus raised the possibility that (P)RR may be related to the central control of water-electrolyte metabolism and blood pressure.

[Effect of AS-35 aerosol on bronchoconstriction induced by specific antigens in macacus rhesus monkeys].

In a previous in vitro study, 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H- pyrido[1,2-a]pyrimidin-4-one (AS-35) was shown to have an inhibitory effect on antigen-induced mediator release and an antagonistic effect on leukotriene C4 and D4 receptors. In the present study, therefore, we investigated the effect of AS-35 aerosol on allergen-induced bronchoconstriction, using 6 female Macacus rhesus monkeys sensitized with DNP-Ascaris extracts (DNP-As). After treatment with an inactive placebo, inhalation challenge with DNP-As increased total lung resistance and decreased dynamic lung compliance dose-dependently 1 week after sensitization with DNP-As. Treatment with AS-35 aerosol, however, significantly inhibited allergen-induced bronchoconstriction dose-dependently 2 weeks after the sensitization. The inhibitory effect was about ten times more potent than that of DSCG. Because we confirmed that DNP-As evoked almost the same bronchoconstriction 1 and 2 weeks after sensitization and also that AS-35 did not inhibit histamine-induced bronchoconstriction at all, we inferred that AS-35 diminished allergen-induced bronchoconstriction by inhibiting allergen-induced mediator release from the cells in the airway.