Dense-core vesicle proteins IA-2 and IA-2{beta} affect renin synthesis and secretion through the {beta}-adrenergic pathway
| Autor: | Yan Qin, Josephine P. Briggs, Jurgen Schnermann, Franziska Theilig, Abner Louis Notkins, Sebastian Bachmann, Soo Mi Kim, Diane Mizel, Hiroki Hirai, Robert Faulhaber-Walter, Tao Cai |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Physiology Blood Pressure Propranolol Biology Kidney Renin-Angiotensin System Mice Internal medicine Renin–angiotensin system Renin medicine Animals Secretion Receptor-Like Protein Tyrosine Phosphatases Class 8 Salt intake Mice Knockout Vesicle Secretory Vesicles Articles Transmembrane protein Juxtaglomerular Apparatus Cell biology Mice Inbred C57BL Endocrinology Knockout mouse Female Adrenergic Fibers medicine.drug Hormone Glomerular Filtration Rate |
| Zdroj: | American journal of physiology. Renal physiology. 296(2) |
| ISSN: | 1931-857X |
| Popis: | IA-2 and IA-2β, 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-2β 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-2β, or both IA-2 and IA-2β 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-2β−/−, and IA-2/IA-2β−/− 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-2β 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-2β−/− mice. Renal tyrosine hydroxylase mRNA and immunoreactivity were reduced in IA-2/IA-2β−/− mice as was the urinary excretion of catecholamines. We conclude that IA-2 and IA-2β 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. |
| Databáze: | OpenAIRE |
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