Regulation of renin secretion by renal juxtaglomerular cells.
A major rate-limiting step in the renin-angiotensin-aldosterone system is the release of active renin from endocrine cells (juxtaglomerular (JG) cells) in the media layer of the afferent glomerular arterioles. The number and distribution of JG cells vary with age and the physiological level of stimulation; fetal life and chronic stimulation by extracellular volume contraction is associated with recruitment of renin-producing cells. Upon stimulation of renin release, labeled renin granules "disappear;" the number of granules decrease; cell membrane surface area increases in single cells, and release is quantal. Together, this indicates exocytosis as the predominant mode of release. JG cells release few percent of total renin content by physiological stimulation, and recruitment of renin cells is preferred to recruitment of granules during prolonged stimulation. Several endocrine and paracrine agonists, neurotransmitters, and cell swelling converge on the stimulatory cyclic AMP (cAMP) pathway. Renin secretion is attenuated in mice deficient in beta-adrenoceptors, prostaglandin E(2)-EP4 receptors, Gsα protein, and adenylyl cyclases 5 and 6. Phosphodiesterases (PDE) 3 and 4 degrade cAMP in JG cells, and PDE3 is inhibited by cyclic GMP (cGMP) and couples the cGMP pathway to the cAMP pathway. Cyclic AMP enhances K(+)-current in JG cells and is permissive for secretion by stabilizing membrane potential far from threshold that activates L-type voltage-gated calcium channels. Intracellular calcium paradoxically inhibits renin secretion likely through attenuated formation and enhanced degradation of cAMP; by activation of chloride currents and interaction with calcineurin. Connexin 40 is necessary for localization of JG cells in the vascular wall and for pressure- and macula densa-dependent suppression of renin release.
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J. B. Winslowsvej 21, 3, 5000, Odense C, Denmark.
Ulla G
UG
Friis
Kirsten
K
Madsen
Jane
J
Stubbe
Pernille B L
PB
Hansen
Per
P
Svenningsen
Peter
P
Bie
Ole
O
Skøtt
Boye L
BL
Jensen
D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System; D055571:Secretory Pathway; D015398:Signal Transduction
D012083:Renin