ArticleAmerican journal of physiology. Renal physiology2013
Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP(3) pathway and the ryanodine receptor.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone.Hypertension (Dallas, Tex. : 1979) · 2014Trial
- A physiology-based mathematical model of the renin-angiotensin system, bone remodeling, and calcium homeostasis: Effects of estrogen and renin-angiotensin system inhibitors.PLoS computational biology · 2026Article
- Calcium-sensing receptor: a potential target for liver health and diseases.Journal of translational medicine · 2025Review
- Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Effect of MgClInternational journal of molecular sciences · 2021Article
- Calcilytic NPS2143 promotes proliferation and inhibits apoptosis of spontaneously hypertensive rat vascular smooth muscle cells via activation of the renin-angiotensin system.Experimental and therapeutic medicine · 2020Article
- CaSR participates in the regulation of vascular tension in the mesentery of hypertensive rats via the PLC‑IP3/AC‑V/cAMP/RAS pathway.Molecular medicine reports · 2019Article
- Calcimimetic R568 reduced the blood pressure and improved aortic remodeling in spontaneously hypertensive rats by inhibiting local renin-angiotensin system activity.Experimental and therapeutic medicine · 2018Article
- Analysis of the calcium paradox of renin secretion.American journal of physiology. Renal physiology · 2018Article
- Localization and function of the renal calcium-sensing receptor.Nature reviews. Nephrology · 2016Review
- Comparative expression of the extracellular calcium-sensing receptor in the mouse, rat, and human kidney.American journal of physiology. Renal physiology · 2016Article
- Article
- The renin-angiotensin-aldosterone system and calcium-regulatory hormones.Journal of human hypertension · 2015Review
- Endothelin inhibits renin release from juxtaglomerular cells via endothelin receptors A and B via a transient receptor potential canonical-mediated pathway.Physiological reports · 2014Article
- Adenosine inhibits renin release from juxtaglomerular cells via an A1 receptor-TRPC-mediated pathway.American journal of physiology. Renal physiology · 2013Article
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5 authors at 2 institutions in 1 country.
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Abstract
The calcium-sensing receptor (CaSR) is a G-coupled protein expressed in renal juxtaglomerular (JG) cells. Its activation stimulates calcium-mediated decreases in cAMP content and inhibits renin release. The postreceptor pathway for the CaSR in JG cells is unknown. In parathyroids, CaSR acts through G(q) and/or G(i). Activation of G(q) stimulates phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP(3)), releasing calcium from intracellular stores. G(i) stimulation inhibits cAMP formation. In afferent arterioles, the ryanodine receptor (RyR) enhances release of stored calcium. We hypothesized JG cell CaSR activation inhibits renin via the PLC/IP(3) and also RyR activation, increasing intracellular calcium, suppressing cAMP formation, and inhibiting renin release. Renin release from primary cultures of isolated mouse JG cells (n = 10) was measured. The CaSR agonist cinacalcet decreased renin release 56 ± 7% of control (P < 0.001), while the PLC inhibitor U73122 reversed cinacalcet inhibition of renin (104 ± 11% of control). The IP(3) inhibitor 2-APB also reversed inhibition of renin from 56 ± 6 to 104 ± 11% of control (P < 0.001). JG cells were positively labeled for RyR, and blocking RyR reversed CaSR-mediated inhibition of renin from 61 ± 8 to 118 ± 22% of control (P < 0.01). Combining inhibition of IP(3) and RyR was not additive. G(i) inhibition with pertussis toxin plus cinacalcet did not reverse renin inhibition (65 ± 12 to 41 ± 8% of control, P < 0.001). We conclude stimulating JG cell CaSR activates G(q), initiating the PLC/IP(3) pathway, activating RyR, increasing intracellular calcium, and resulting in calcium-mediated renin inhibition.
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