Renal interstitial Ca<sup>2+</sup>

Mupanomunda, Maria; Tian, Bing; Ishioka, Norio; Bukoski, Richard D.

doi:10.1152/ajprenal.2000.278.4.f644

Cited by 28 publications

(40 citation statements)

References 23 publications

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“…Mupanomunda et al (25) has shown that renal cortical interstitial calcium concentration may actually vary normally over surprisingly wide ranges, consistent with the concentrations we have used. Thus, our observations suggest that PDE1C may contribute to the overall balance of cAMP formation in the JG cell under normal physiologic circumstances and that the JG cell CaSR may serve as an important conduit pathway (29), linking changes in the extracellular calcium with a calcium-mediated balance of cAMP metabolism and synthesis within the cell.…”

Section: Discussionsupporting

confidence: 89%

“…We used both the normal 1.2 mM Ca in the media reflecting normal renal cortical interstitial free Ca concentration (25), as well as a reduced but still physiological Ca concentration of 0.9 mM as an established technique to amplify basal renin release (4) so as to exaggerate any inhibitory response to activation of the CaSR. In each case, compounds were tested using a primary culture of JG cells; either without or after the addition of 1 M of the CaSR agonist cinacalcet (Sensipar; Amgen, Thousand Oaks, CA; n ϭ 16) (28,29).…”

Section: Inhibition Of Pde Activitymentioning

confidence: 99%

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Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells

Ortiz-Capisano

Liao

Ortíz

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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release from the juxtaglomerular (JG) cell is stimulated by the second messenger cAMP and inhibited by calcium. We previously showed JG cells contain a calcium sensing receptor (CaSR), which, when stimulated, decreases cAMP formation and inhibits renin release. We hypothesize CaSR activation decreases cAMP and renin release, in part, by stimulating a calcium calmodulin-activated phosphodiesterase 1 (PDE1). We incubated our primary culture of JG cells with two selective PDE1 inhibitors [8-methoxymethil-IBMX (8-MM-IBMX; 20 M) and vinpocetine (40 M)] and the calmodulin inhibitor W-7 (10 M) and measured cAMP and renin release. Stimulation of the JG cell CaSR with the calcimimetic cinacalcet (1 M) resulted in decreased cAMP from a basal of 1.13 Ϯ 0.14 to 0.69 Ϯ 0.08 pM/mg protein (P Ͻ 0.001) and in renin release from 0.89 Ϯ 0.16 to 0.38 Ϯ 0.08 g ANG I/ml ⅐ h Ϫ1 ⅐ mg protein Ϫ1 (P Ͻ 0.001). However, the addition of 8-MM-IBMX with cinacalcet returned both cAMP (1.10 Ϯ 0.19 pM/mg protein) and renin (0.57 Ϯ 0.16 g ANG I/ml ⅐ h Ϫ1 ⅐ mg protein Ϫ1 ) to basal levels. Similar results were obtained with vinpocetine, and also with W-7. Combining 8-MM-IBMX and W-7 had no additive effect. To determine which PDE1 isoform is involved, we performed Western blot analysis for PDE1A, B, and C. Only Western blot analysis for PDE1C showed a characteristic band apparent at 80 kDa. Immunofluorescence showed cytoplasmic distribution of PDE1C and renin in the JG cells. In conclusion, PDE1C is expressed in isolated JG cells, and contributes to calcium's inhibitory modulation of renin release from JG cells.angiotensin; calmodulin; phosphodiesterase; cAMP; adenylyl cyclase RENIN IS THE RATE-LIMITING enzymatic step in the production of angiotensin, a hormone that integrates cardiovascular and renal function in the control of blood pressure as well as salt and volume homeostasis (33). Renin is produced by, stored in, and released from juxtaglomerular (JG) cells, which are derived from renin progenitor cells (42) and are located in the afferent arteriole near the hilus of the glomerulus (2, 43, 35). Two main intracellular second messenger systems are known to regulate renin synthesis and secretion: the cyclic nucleotide, cyclic adenosine monophosphate (cAMP) (8, 41), and intracellular calcium (Ca) (21).Renin secretion by the JG cells demonstrates a paradoxical inverse relationship with intracellular calcium concentration, such that millimolar changes in extracellular Ca or micromolar elevations in intracellular calcium retard renin release (1,9,14,20,22). The primary second messenger involved in the regulation of renin release is cAMP (8), and the concentration of cAMP in cells is determined by a balance between the rate of cAMP generation by adenylyl cyclases and cAMP hydrolysis by phosphodiesterases (PDE) (7, 16). We (30, 31), and also Grünberger et al. (18), have reported JG cells express calciuminhibitable adenylyl cyclase (27). Furthermore, we have identified the JG-specific isoform-regulating renin release to be adenylyl cyclase type V (30)...

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Section: Discussionsupporting

confidence: 89%

Section: Inhibition Of Pde Activitymentioning

confidence: 99%

Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells

Ortiz-Capisano

Liao

Ortíz

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Bukoski, 2001, unpublished observations), which is well within the range of the concentrations that have been shown to occur in the interstitial fluid compartment of the small bowel 16 and renal cortex. 17 The relaxation is attenuated by sensory denervation and correlates with the presence of Ca 2ϩ receptor-positive nerve fibers. 2 Ca 2ϩ -induced relaxation of rat arteries has also been shown to be inhibited by blockers of the large conductance K Ca channel 4,5 and by SR141716A 4 , a compound with CB 1 antagonist activity.…”

Section: Discussionmentioning

confidence: 99%

CB ₁ Receptor Antagonist SR141716A Inhibits Ca ²⁺ -Induced Relaxation in CB ₁ Receptor-Deficient Mice

et al. 2002

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Abstract-Mesenteric branch arteries isolated from cannabinoid type 1 receptor knockout (CB 1 Ϫ/Ϫ ) mice, their wild-type littermates (CB 1 ϩ/ϩ mice), and C57BL/J wild-type mice were studied to test the hypothesis that murine arteries undergo high sensitivity Ca 2ϩ -induced relaxation that is CB 1 receptor dependent. Confocal microscope analysis of mesenteric branch arteries from wild-type mice showed the presence of Ca 2ϩ receptor-positive periadventitial nerves. Arterial segments of C57 control mice mounted on wire myographs contracted in response to 5 mol/L norepinephrine and responded to the cumulative addition of extracellular Ca 2ϩ with a concentration-dependent relaxation that reached a maximum of 72.0Ϯ6.3% of the prerelaxation tone and had an EC 50 for Ca 2ϩ of 2.90Ϯ0.54 mmol/L. The relaxation was antagonized by precontraction in buffer containing 100 mmol/L K ϩ and by pretreatment with 10 mmol/L tetraethylammonium. Arteries from CB 1 Ϫ/Ϫ and CB 1 ϩ/ϩ mice also relaxed in response to extracellular Ca 2ϩ with no differences being detected between the knockout and their littermate controls. SR141716A, a selective CB 1 antagonist, caused concentration-dependent inhibition of Ca 2ϩ -induced relaxation in both the knockout and wild-type strains (60% inhibition at 1 mol/L). O-1918, a cannabidiol analog, had a similar blocking effect in arteries of both wild-type and CB 1 Ϫ/Ϫ mice at 10 mol/L. In contrast, 1 mol/L SR144538, a cannabinoid type 2 receptor antagonist, or 50 mol/L 18␣-glycyrrhetinic acid, a gap junction blocker, were without effect. SR141716A (1 to 30 mol/L) was also assessed for nonspecific actions on whole-cell K ϩ currents in isolated vascular smooth muscle cells. SR141716A inhibited macroscopic K ϩ currents at concentrations higher than those required to inhibit Ca 2ϩ -induced relaxation, and appeared to have little effect on currents through large conductance Ca 2ϩ -activated K ϩ channels. These data indicate that arteries of the mouse relax in response to cumulative addition of extracellular Ca 2ϩ in a hyperpolarization-dependent manner and rule out a role for CB 1 or CB 2 receptors in this effect. The possible role of a nonclassical cannabinoid receptor is discussed. (Hypertension. 2002;39:251-257.) Key Words: mesenteric arteries Ⅲ calcium Ⅲ relaxation Ⅲ potassium channels O ver the past several years, a novel, extracellular Ca 2ϩ -activated, vasodilator pathway has been described in isolated rat arteries. The current model describing this system holds that elevation of extracellular Ca 2ϩ , as occurs in the interstitial compartments of some tissues, activates a Ca 2ϩ -sensing receptor localized on perivascular sensory nerves. Activation of this receptor causes the release of a transmitter that diffuses to underlying vascular smooth muscle and induces hyperpolarization-mediated relaxation through activation of a vascular smooth muscle cannabinoid type 1 (CB 1 ) receptor. 1 Among the findings that support this pathway are the demonstration that dorsal root ganglia and perivascular sensory nerv...

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“…In fact, the CaR has been shown to detect small changes in Ca 2+ e 13 , and small increases in [Ca 2+ ]IF that are within the physiological range 14 . In situ microdialysis studies measuring [Ca 2+ ]IF in the duodenal submucosa and kidney cortex, two tissues that are essential for the regulation of peripheral resistance and blood pressure (BP), showed dynamic changes as a function of the gut lumen [Ca 2+ ].…”

Section: Discussionmentioning

confidence: 99%

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography

Bridges

Williams

Pointer

et al. 2011

JoVE

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Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. These small vessels of between 100-400 μm in diameter function primarily in directing blood flow to various organs according to the overall requirements of the body. The rat mesenteric artery has a diameter greater than 100 μm. The myography technique, first described by Mulvay and Halpern 1 , was based on the method proposed by Bevan and Osher 2 . The technique provides information about small vessels under isometric conditions, where substantial shortening of the muscle preparation is prevented. Since force production and sensitivity of vessels to different agonists is dependent on the extent of stretch, according to active tension-length relation, it is essential to conduct contraction studies under isometric conditions to prevent compliance of the mounting wires. Stainless steel wires are preferred to tungsten wires because of oxidation of the latter, which affects recorded responses 3 .The technique allows for the comparison of agonist-induced contractions of mounted vessels to obtain evidence for normal function of vascular smooth muscle cell receptors.We have shown in several studies that isolated mesenteric arteries that are contracted with phenylyephrine relax upon addition of cumulative concentrations of extracellular calcium (Ca 2+ e). The findings led us to conclude that perivascular sensory nerves, which express the G protein-coupled Ca 2+ -sensing receptor (CaR), mediate this vasorelaxation response. Using an automated wire myography method, we show here that mesenteric arteries from Wistar, Dahl salt-sensitive(DS) and Dahl salt-resistant (DR) rats respond differently to Ca 2+ e. Tissues from Wistar rats showed higher Ca 2+ -sensitivity compared to those from DR and DS. Reduced CaR expression in mesenteric arteries from DS rats correlates with reduced Ca 2+ e-induced relaxation of isolated, pre-contracted arteries. The data suggest that the CaR is required for relaxation of mesenteric arteries under increased adrenergic tone, as occurs in hypertension, and indicate an inherent defect in the CaR signaling pathway in Dahl animals, which is much more severe in DS.The method is useful in determining vascular reactivity ex vivo in mesenteric resistance arteries and similar small blood vessels and comparisons between different agonists and/or antagonists can be easily and consistently assessed side-by-side 6,7,8 . Video LinkThe video component of this article can be found at http://www.jove.com/details.php?id=3119 2. Perform a mid-line laparotomy to expose mesenteric bed. 3. Using scissors, remove about 85 cm of intestine with feeding vasculature with the superior mesenteric artery. Cut the proximal end of intestinal section close to the pylorus and the distal end near the ileo-coecal junction. Segments of the intestine are isolated from rats that are deeply anesthetized with isoflurane and euthanized by open-chest cardiac puncture. 4. Placed excised section in a coated petri dish ...

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Renal interstitial Ca²⁺

Cited by 28 publications

References 23 publications

Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells

Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells

CB ₁ Receptor Antagonist SR141716A Inhibits Ca ²⁺ -Induced Relaxation in CB ₁ Receptor-Deficient Mice

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography

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Renal interstitial Ca2+

Cited by 28 publications

References 23 publications

Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells

Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells

CB 1 Receptor Antagonist SR141716A Inhibits Ca 2+ -Induced Relaxation in CB 1 Receptor-Deficient Mice

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography

Contact Info

Product

Resources

About

Renal interstitial Ca²⁺

CB ₁ Receptor Antagonist SR141716A Inhibits Ca ²⁺ -Induced Relaxation in CB ₁ Receptor-Deficient Mice