Identification of insulin-regulated aminopeptidase (IRAP) in the rat pineal gland and the modulation of melatonin synthesis by angiotensin IV

Author(s):Show less -

Abrahao, Mariana Vieira ^[1] ; Teixeira dos Santos, Natalia Fernanda ^[1] ; Tatagiba Kuwabara, Wilson Mitsuo ^[2] ; do Amaral, Fernanda Gaspar ^{[2, 3]} ; Buonfiglio, Daniella do Carmo ^[2] ; Peres, Rafael ^[2] ; Alponti Vendrame, Rafaela Fadoni ^[1] ; da Silveira, Paulo Flavio ^[1] ; Cipolla-Neto, Jose ^[2] ; Baltatu, Ovidiu Constantin ^[4] ; Afeche, Solange Castro ^[1]

Affiliation

^[1] Butantan Inst, Lab Pharmacol, Av Vital Brazil 1500, BR-05503000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Physiol, BR-04023901 Sao Paulo, SP - Brazil

^[4] Laureate Int Univ, Anhembi Morumbi Univ, CITE, BR-12247016 Sao Jose Dos Campos, SP - Brazil

• Document type: Journal article
• Source: Brain Research; v. 1704, p. 40-46, FEB 1 2019.
• Web of Science Citations: 1

Abstract

A local renin-angiotensin system (RAS) has been postulated in the pineal gland. In addition to angiotensin II (Ang II), other active metabolites have been described. In this study, we aimed to investigate a role for Ang IV in melatonin synthesis and the presence of its proposed (IRAP)/AT(4) receptor (insulin-regulated aminopeptidase) in the pineal gland. The effect of Ang IV on melatonin synthesis was investigated in vitro using isolated pinealocytes. IRAP protein expression and activity were evaluated by Western blot and fluorimetry using Leu-4Me-beta-naphthylamide as a substrate. Melatonin was analyzed by HPLC, calcium content by confocal microscopy and cAMP by immunoassay. Ang IV significantly augmented the NE-induced melatonin synthesis to a similar degree as that achieved by Ang This Ang IV effect in pinealocytes appears to be mediated by an increase in the intracellular calcium content but not by cAMP. The (IRAP)/AT(4) expression and activity were identified in the pineal gland, which were significantly higher in membrane fractions than in soluble fractions. Ang IV significantly reduced IRAP activity in the pineal membrane fractions. The main findings of the present study are as follows: (1) Ang IV potentiates NE-stimulated melatonin production in pinealocytes, (2) the (TRAP)/AT(4) receptor is present in the rat pineal gland, and (3) Ang IV inhibits IRAP activity and increases pinealocytes {[}Ca2+](i). We conclude that Ang IV is an important component of RAS and modulates melatonin synthesis in the rat pineal gland. (AU)

• FAPESP's process: 07/07682-9 - Melatonin synthesis in the pineal gland: modulation by angiotensins III and IV
• Grantee: Solange Castro Afeche
• Support Opportunities: Regular Research Grants