Comparison of the contractile effects and binding kinetics of endothelin‐1 and sarafotoxin S6b in rat isolated renal artery

Devadason, Peter S S; Henry, Peter J.

doi:10.1038/sj.bjp.0701126

Cited by 21 publications

(16 citation statements)

References 38 publications

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“…31 ET B receptors have also been detected in be explained in terms of differences in the kinetics of ovine airway smooth muscle cells in culture, 56 although particular receptor-ligand interactions. 54 In the abthis is related to passage-associated cell phenotype sence of support from molecular cloning, structural, changes. 57 In contrast, ET A and ET B receptors were operational and signal transduction data, the conpresent in approximately equal proportions in rat clusion that such subtypes exist must be viewed as and mouse isolated airway smooth muscle and both unproven.…”

Section: Et Receptor/ligand Interactionsmentioning

confidence: 99%

Endothelin Receptor Subtypes: Distribution and Function in the Lung

Goldie

1998

Pulmonary Pharmacology & Therapeutics

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Section: Et Receptor/ligand Interactionsmentioning

confidence: 99%

Endothelin Receptor Subtypes: Distribution and Function in the Lung

Goldie

1998

Pulmonary Pharmacology & Therapeutics

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“…Recent research in isolated, hydronephrotic kidneys has provided evidence that ET A receptors are important for constriction of preglomerular vessels, whilst ET B receptors are important for mediating constriction of both preglomerular vessels and efferent arterioles ( Endlich et al ., 1996 ). In isolated, main branches of the renal artery, in vitro studies have demonstrated the presence of ET A receptors and absence of ET B receptors ( Clark & Pierre, 1995 ; Devadason & Henry, 1997 ).…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological effects of endothelin‐1 and their relationship to contraction in rat renal arterial smooth muscle

Betts

Kozlowski

2000

British J Pharmacology

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1 The electophysiological e ects of endothelin-1 (ET-1) and their relationship to contraction remain unclear in the renal circulation. Using endothelium-denuded arteries from the main branch of the renal artery proximal to the kidney of the rat, we have examined its e ects on tension and conducted parallel patch-clamp measurements using freshly isolated smooth muscle cells from this tissue.2 Pharmacological experiments revealed that ET-1 produced constriction of renal arteries dependent on the in¯ux of extracellular Ca 2+ , mediated solely through ET A receptor stimulation. 3 Current-clamp experiments revealed that renal arterial myocytes had a resting membrane potential of *32 mV, with the majority of cells exhibiting spontaneous transient hyperpolarizations (STHPs). Application of ET-1 produced depolarization and in those cells exhibiting STHPs, either caused their inhibition or made them occur regularly. 4 Under voltage-clamp conditions cells were observed to exhibit spontaneous transient outward currents (STOCs) inhibited by iberiotoxin. Application of voltage-ramps revealed an outward current activated at *730 mV, sensitive to both 4-AP and TEA. Taken together these results suggest that renal arterial myocytes possess both delayed rectifying K + (K V ) and Ca 2+ -activated K + (BK Ca ) channels. 5 Under voltage-clamp, ET-1 attenuated the outward current and reduced the magnitude and incidence of STOCs: e ects mediated solely as a consequence of ET A receptor stimulation. 6 Thus, in conclusion, activation of ET A receptors by ET-1 causes inhibition of K V and BK Ca channel activity, which could promote and/or maintain membrane depolarization. This e ect is likely to favour L-type Ca 2+ channel activity providing an in¯ux pathway for extracellular Ca 2+ essential for contraction.

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“…Functional ET-1 receptors have been characterized in the rat renal vasculature. In the isolated rat main branch of the renal artery, the contraction to ET-1 is mediated by ET A receptors, whereas ET B receptors do not appear to be present [32,33]. However, from in vivo studies, there is evidence that both ET A and ET B receptors contribute to the constriction of the rat renal microvasculature [34].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms Underlying the Contractile Response to Endothelin-1 in the Rat Renal Artery

Callera¹,

Bendhack²

2003

Pharmacology

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We assessed the functional response and the mechanisms following receptor stimulation of endothelin-1 (ET-1) in the rat renal artery. In this study, isometric tension was recorded in renal artery rings without endothelium. Cumulative application of ET-1 from 0.1 to 100 nmol/l induced a sustained concentration-dependent contraction in the renal artery. Submaximal contraction induced by 10 nmol/l ET-1 in 2.5 mmol/l Ca²⁺ and in the absence of inhibitors was used as control response (100%). The relative contribution of different sources of Ca²⁺ in ET-1-induced contraction was evaluated. The contractile response to 10 nmol/l ET-1 in 2.5 mmol/l Ca²⁺(1.2 ± 0.2 g) was significantly inhibited either in Ca²⁺-free solution containing 100 µmol/l ethylene glycol bis-(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (0.6 ± 0.1 g) or after depletion of intracellular Ca²⁺ stores (0.62 ± 0.05 g). The contribution of phospholipase C and protein kinase C was evaluated by using their inhibitors 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC) and [1-(5-isoquinolinesulfonyl)-2-methylpiperazine] (H-7), respectively. The contractile response to 10 nmol/l ET-1 was inhibited by 10 µmol/l NCDC (to 80 ± 6%) and 30 µmol/l H-7 (to 76.6 ± 6.5%). We found that 1 µmol/l nifedipine inhibited the ET-1-induced contraction (to 48.7 ± 6.9%), indicating the contribution of Ca²⁺ influx through voltage-gated L-type Ca²⁺ channels to this response. Further, the inhibitory effect of nifedipine was to a greater extent as compared with NCDC or H-7. Additive inhibition of ET-1-induced contraction was not observed in the presence of both nifedipine and NCDC. We also evaluated the role of the ionic transport system in the ET-1-induced response by using 20 nmol/l 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an inhibitor of Na⁺-H⁺ exchange, or 100 µmol/l ouabain, an inhibitor of Na⁺-K⁺-ATPase. The response to ET-1 was decreased by both EIPA (to 61.6 ± 8.4%) and ouabain (to 62.1 ± 8.6%). The contribution of Na⁺-Ca²⁺ exchange to ouabain action was tested using the inhibitor dimethyl amiloride HCl (10 µmol/l). The decrease in ET-1-induced contraction by the combination of ouabain and dimethyl amiloride HCl was similar to that observed with ouabain alone. In view of these observations, both extra- and intracellular sources of Ca²⁺ contribute to the contractile response induced by ET-1 in the renal artery. Our findings also revealed the importance of Ca²⁺ influx through voltage-gated L-type Ca²⁺ channels in mediating contraction to ET-1 in the renal artery, whereas a minor role of phospholipase C and protein kinase C was observed. Na⁺-H⁺ exchange and Na⁺-K⁺-ATPase also play a role in the ET-1-induced contraction in renal artery. Moreover, the contribution of Na⁺-K⁺-ATPase in ET-1 contraction is not an Na⁺-Ca²⁺

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Comparison of the contractile effects and binding kinetics of endothelin‐1 and sarafotoxin S6b in rat isolated renal artery

Cited by 21 publications

References 38 publications

Endothelin Receptor Subtypes: Distribution and Function in the Lung

Endothelin Receptor Subtypes: Distribution and Function in the Lung

Electrophysiological effects of endothelin‐1 and their relationship to contraction in rat renal arterial smooth muscle

Mechanisms Underlying the Contractile Response to Endothelin-1 in the Rat Renal Artery

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