Characterization of endothelin 1 receptor and signal transduction mechanisms in rat medullary interstitial cells

Wilkes, Barry M.; Ruston, A. S.; Mento, P. F.; Girardi, Erika; Hart, Deborah; Molen, M. Vander; Barnett, Richard; Nord, Edward P.

doi:10.1152/ajprenal.1991.260.4.f579

Cited by 38 publications

(49 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…H7, a protein kinase C inhibitor, had no effect on unstimulated RMIC surface area, but completely blocked the contractile response to ET-1. Hence, ET-1 stimulated RMIC contraction is dependent in part on voltage-insensitive extracellular calcium entry -and is mediated through activation of protein kinase C. ET-1 stimulates RMIC production of PGE2 (13,22), an eicosanoid which can inhibit the vasoconstrictive effect of ET-1 (23). To determine if cyclooxygenase products modify the contractile response to ET-1 in RMIC, cells were treated with indomethacin followed by addition of ET-1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…ET-1 is a 21-amino acid peptide that is the most potent vasoconstrictor known (17). It binds to high affinity receptors on RMIC and elicits an increase in cytosolic-free Ca2+ concentration that is dependent in part upon increases in inositol trisphosphate levels and receptor-operated Ca2+ channels (13). We report that ET-1 causes a long-lasting and potent contraction of cultured rat RMIC.…”

Section: Introductionmentioning

confidence: 84%

“…These include atrial natriuretic factor (9), nitric oxide (10), angiotensin I (4,11), bradykinin (4), vasopressin (4,12), and endothelin-1 (ET-1 ) (13). Because of ongoing research interest by this laboratory in the production and actions of ET-1 in the renal medulla (14-16), we chose to examine the effect of this peptide on RMIC contraction.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of a contractile function for renal medullary interstitial cells.

Hughes¹,

Barry²,

Kohan³

1995

J. Clin. Invest.

View full text Add to dashboard Cite

Renomedullary interstitial cells (RMIC) are unique to the renal medulla. By virtue of their anatomic location and arrangement, RMIC may hinder axial dissipation of the concentration gradient, thereby aiding urinary concentration. A more active role in urinary concentration has been postulated on the basis of speculations about RMIC contractile potential, however, RMIC contraction has not been investigated. To determine if these cells are contractile, cultured rat RMIC were exposed to endothelin-1 (ET-1), a potent vasoconstrictor which binds to RMIC, and examined using video microscopy. ET-1 (as low as 10 pM) caused a slowly developing and dose-dependent reduction in RMIC surface area. ET-1 markedly increased the number and intensity of F-actin microfilament staining. ET-1-induced RMIC contraction was not altered by nifedipine, was partially reduced by nickel, and was completely inhibited by H7, indicating that ET-1 action is mediated by protein kinase C and is partially dependent upon receptor-operated calcium channels. The ET-1 effect does not involve nitric oxide since NGmonomethyl-L-argiinine did not alter ET-1-induced RMIC contraction; in addition, ET-1 had only a minor effect on cGMP levels and no effect on nitrite production. PGE2 acts in an autocrine manner to dampen ET action since indomethacin potentiates, while PGE2 inhibits, ET-1-induced RMIC contraction. The contractile response is not unique to ET-1 since vasopressin also reduces RMIC surface area and increases F-actin microfiliment staining. These studies demonstrate that RMIC in culture are contractile. The possibility is raised that contraction of RMIC plays a role in modifying urinary concentration as well as regulation of other renal medullary functions. (J. Clin. Invest. 1995. 96:411-416.)

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a contractile function for renal medullary interstitial cells.

Hughes¹,

Barry²,

Kohan³

1995

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…First of all, there is scarce information on the two ET receptor subtypes' role in the kidney, and the available evidence is conflicting. On the one hand, results from radioligand binding ( 17), as well as mRNA measurements ( 18), suggest that ETA receptors are located primarily on vascular smooth muscle cells and ETB receptors are found on the tubular epithelial cells. In contrast, there is emerging evidence from whole animal studies with selective agonists and antagonists of ETA and ETB receptors, indicating that at least in the rat, renal vasoconstriction is not mediated by the ETA receptor ( 19,20).…”

Section: Discussionmentioning

confidence: 99%

Reversal of postischemic acute renal failure with a selective endothelinA receptor antagonist in the rat.

Gellai¹,

Jugus²,

Fletcher³

et al. 1994

J. Clin. Invest.

199

View full text Add to dashboard Cite

Studies were designed to examine the effect of a selective endothelinA (ETA) receptor antagonist, BQ123, on severe postischemic acute renal failure (ARF) in Sprague-Dawley rats. Severe ARF was induced in uninephectomized, chronically instrumented rats by 45-min renal artery occlusion. BQ123 (0.1 mg/kg. min) or vehicle was infused intravenously for 3 h on the day after ischemia. Measurements before infusion (24 h control) showed a 98% decrease in glomerular filtration rate (GFR), increase in fractional excretion of sodium from 0.6 to 39%, and in plasma K+ from 4.3 to 6.5 mEq/liter. All vehicletreated rats died in 4 d because of continuous deterioration of renal function, resulting in an increase of plasma K+ to fatal levels (> 8 mEq/liter). Infusion of BQ123 significantly improved survival rate (75%) by markedly improving tubular reabsorption of Na' and moderately increasing GFR and K+ excretion. Plasma K+ returned to basal levels by the 5th d after ischemia. Improved tubular function was followed by gradual recovery in GFR and urinary concentrating mechanism.Additional data from renal clearance studies in rats with moderate ARF (30-min ischemia) and in normal rats with intact kidneys showed that ETA receptor blockade increases Nan reabsorption and has no effect on renal hemodynamics. These results indicate that in the rat, the ETA receptor subtype mediates tubular epithelial function, and it plays a significant role in the pathogenesis of ischemia-induced ARF. Treatment with the selective ETA receptor antagonist reverses deteriorating tubular function in established ARF, an effect of possible therapeutic significance. (J. Clin. Invest. 1994. 93:900-906.) Key words: ischemia * moderate and severe acute renal failure * endothelinA receptor * BQ123

show abstract

“…The highest concentrations of immunoreactive ET-1 in the body have been detected in the renal medulla (23). In addition, gene expression and immunoreactive peptides of ET-1 and its receptors have been demonstrated in the renal tissue, especially in the medullary region (23,26,40,42,45). Interestingly, in vivo studies revealed that administration of ET-1 resulted in reduced renal hemodynamics and kidney dysfunction, similar to those found during pneumoperitoneum (9).…”

mentioning

confidence: 90%

Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

Abassi

Bishara²,

Karram³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

The mechanism underlying this phenomenon is largely unknown. This study was designed to investigate the involvement of endothelin (ET)-1 and nitric oxide (NO) systems in IAP-induced renal dysfunction. Rats were subjected to IAP of 14 mmHg for 1 h, followed by a deflation for 60 min (recovery). Four additional groups were pretreated with 1) ABT-627, an ET A antagonist; 2) A-192621, an ETB antagonist; 3) nitroglycerine; and 4) N G -nitro-L-arginine methyl ester, a NO synthase inhibitor, before IAP. Urine flow rate (V), absolute Na ϩ excretion (UNaV), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. Significant reductions in kidney function and hemodynamics were observed when IAP was applied. V decreased from 8.1 Ϯ 1.0 to 5.8 Ϯ 0.5 l/min, UNaV from 1.08 Ϯ 0.31 to 0.43 Ϯ 0.10 eq/min, GFR from 1.84 Ϯ 0.12 to 1.05 Ϯ 0.06 ml/min (Ϫ46.9 Ϯ 2.7% from baseline), and RPF from 8.62 Ϯ 0.87 to 3.82 Ϯ 0.16 ml/min (Ϫ54 Ϯ 3.5% from baseline). When the animals were pretreated with either ABT-627 or A-192621, given alone or combined, the adverse effects of IAP on GFR, RPF, V, and UNaV were significantly augmented. When the animals were pretreated with nitroglycerine, the adverse effects of pneumoperitoneum on GFR and RPF were substantially improved. In contrast, pretreatment with N G -nitro-L-arginine methyl ester remarkably aggravated pneumoperitoneum-induced renal dysfunction. In conclusion, decreased renal excretory function and hypofiltration are induced by increased IAP. These effects are related to impairment of renal hemodynamics and could be partially ameliorated by pretreatment with nitroglycerine and aggravated by NO and ET blockade.rat; intra-abdominal pressure PNEUMOPERITONEUM AT PRESSURE above 10 mmHg during laparoscopic surgery has been shown to produce transient oliguria and reduced glomerular filtration rate (GFR) and renal blood flow (RBF) (3,9,16,33,34). Despite much research in this field, the systemic physiological consequences of CO 2 pneumoperitoneum and the mechanisms underlying its adverse effects on renal hemodynamics and excretory function are not fully understood (9). However, there is compelling experimental evidence that the adverse renal effects induced by pneumoperitoneum are affected by the level of intra-abdominal pressure (IAP), volume status, degree of hypercarbia, positioning, and individual hemodynamic and renal reserves (9, 10). Additional factors that may affect renal function during pneumoperitoneum include direct compression of the renal parenchyma and renal vein (4, 17), increased resistance in the renal vasculature (47), and release of vasoconstrictors, such as vasopressin, angiotensin II, catecholamines, and endothelin (ET)-1 (1, 13). The latter is a very potent natural mammalian vasoconstrictor agent (25), acting on the cardiovascular and renal systems and other target organs by binding to two major types of receptors, ET A and ET B (2,25,36). High abundance of ET A receptors has been detected in the aorta, heart, and kidney, whereas ET B receptors are expre...

show abstract

Characterization of endothelin 1 receptor and signal transduction mechanisms in rat medullary interstitial cells

Cited by 38 publications

References 0 publications

Identification of a contractile function for renal medullary interstitial cells.

Identification of a contractile function for renal medullary interstitial cells.

Reversal of postischemic acute renal failure with a selective endothelinA receptor antagonist in the rat.

Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

Contact Info

Product

Resources

About