Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (AII) regulation of renin production by the juxtaglomerular (JG) cells of the kidney is commonly thought to occur through a direct feedback mechanism. However, recent evidence suggests that other cells in the vicinity may indirectly mediate AII's effect on renin production. Therefore we investigated whether an in vitro model of JG cells (As4.1) could have intercellular communication with endothelial or smooth muscle cells, which are in proximity to JG cells in vivo. 6-carboxyfluorescein was introduced to individual bovine aortic endothelial cells in co-culture with As4.1 cells. Coupling was observed 84% of the time at resting membrane potential and was attenuated by membrane depolarization or octanol (1 mM). Calcein green transfer between human aortic smooth muscle and As4.1 cells occurred 82% of the time and was inhibited by octanol. Expression of connexin 37, 40, 43, and 45 were detected in As4.1 cells using RT-PCR. Stimulation of As4.1 cells by AII failed to alter [Ca(2+)](i) or renin mRNA levels. These findings support the existence of gap junctions between renin producing cells and other cell types of the JG region. Moreover the lack of effect by AII suggest that feedback regulation of renin by AII may be due in part to intercellular communication with cells in proximity to JG cells.
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PMID:Intercellular communication between renin expressing As4.1 cells, endothelial cells and smooth muscle cells. 1257 Sep 29

The juxtaglomerular areas of mammalian kidneys express the gap junction proteins connexin 37, 40, 43, and 45. Among these, Cx40 plays a major role for the function of juxtaglomerular renin-expressing cells, while Cx37 and Cx45 appear to be less relevant in this context. Since the role of the remaining Cx43 for the function of renin expression is not well understood, this study aimed to systematically characterize the direct role of Cx43 for renin expression and secretion. For this aim, we generated mice with endothelium and with renin cell-specific deletions of Cx43, and we characterized the regulation of renin expression and renin secretion in the kidneys of these mice on normal salt diet and during chronic challenge of the renin system by pretreatment of mice with a low-salt diet in combination with an angiotensin I-converting enzyme inhibitor. We found that renal renin mRNA abundance, plasma renin concentration, and systolic blood pressure did not differ between wild-type, Cx43(fl/fl) Ren1d(+/Cre) mice as well as Cx43(fl/fl) Tie-2(+/Cre) mice under basal conditions nor under chronic stimulation by salt depletion. The localization of renin-expressing cells was also regular in kidneys of all genotypes, and moreover, regulation of renin secretion by beta-adrenergic stimulation and renal perfusion pressure measured in isolated perfused kidneys of Cx43(fl/fl) Ren1d(+/Cre) and Cx43(fl/fl) Tie-2(+/Cre) mice was not different from control. We infer from these results that Cx43 plays if at all only a minor role for the functional control of renin-producing cells in the kidney.
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PMID:Connexin 43 is not essential for the control of renin synthesis and secretion. 2406 52