Open AccessDense-core vesicle proteins IA-2 and IA-2β affect renin synthesis and secretion through the β-adrenergic pathway
Author(s) -
Soo Mi Kim,
Franziska Theilig,
Yan Qin,
Tao Cai,
Diane Mizel,
Robert Faulhaber-Walter,
Hiroki Hirai,
S. Bachmann,
Josephine P. Briggs,
Abner Louis Notkins,
Jürgen Schnermann
Publication year - 2009
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.335
H-Index - 169
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.90543.2008
Subject(s) - medicine , endocrinology , renin–angiotensin system , aldosterone , plasma renin activity , chemistry , secretion , angiotensin ii , tyrosine hydroxylase , kidney , biology , dopamine , blood pressure
IA-2 and IA-2beta, major autoantigens in type 1 diabetes, are transmembrane proteins in dense-core vesicles, and their expression influences the secretion of hormones and neurotransmitters. The present experiments were performed to examine whether IA-2 and IA-2beta modulate the release of renin from dense-core vesicles of juxtaglomerular granular cells in the kidney. Plasma renin concentration (PRC; ng angiotensin I.ml(-1).h(-1)) was significantly reduced in mice with null mutations in IA-2, IA-2beta, or both IA-2 and IA-2beta compared with wild-type mice (876 +/- 113, 962 +/- 130, and 596 +/- 82 vs. 1,367 +/- 93; P < 0.01, P < 0.02, and P < 0.001). Renin mRNA levels were reduced to 26.4 +/- 5.1, 39 +/- 5.4, and 35.3 +/- 5.5% of wild-type in IA-2-/-, IA-2beta-/-, and IA-2/IA-2beta-/- mice. Plasma aldosterone levels were not significantly different among genotypes. The regulation of PRC by furosemide and salt intake, and of aldosterone by salt intake, was maintained in all genotypes. IA-2 and IA-2beta expression did not colocalize with renin but showed overlapping immunoreactivity with tyrosine hydroxylase. While propranolol reduced PRC in wild-type mice, it had no effect on PRC in IA-2/ IA-2beta-/- mice. Renal tyrosine hydroxylase mRNA and immunoreactivity were reduced in IA-2/IA-2beta-/- mice as was the urinary excretion of catecholamines. We conclude that IA-2 and IA-2beta are required to maintain normal levels of renin expression and renin release, most likely by permitting normal rates of catecholamine release from sympathetic nerve terminals.