Effects of Endothelin Receptor Selective Antagonists, BQ-123 and BQ-788, on IRL 1620 and Endothelin-1 Responses of Airway and Vascular Preparations from Rats

O’Donnell, Stella R.; Kay, C.S.

doi:10.1006/pulp.1995.1002

Cited by 12 publications

(16 citation statements)

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“…The results from the present insubsequently found to be decreased. 46 In contrast, vestigation, which are in accordance with those from however, chronic hypoxia actually increases the level previous studies conducted upon rat isolated of ET A receptor mRNA in whole rat lung and raises trachea, 13,16 suggest that both ET A and ET B receptors the level of ET B receptor mRNA in the rat main are involved in mediating contraction in rat trachea. pulmonary artery but does not change ET A receptor This finding is not unique to rat airways; in human mRNA in these vessels.…”

Section: Discussionsupporting

confidence: 78%

“…29 It is not known if an inhibitory ET A receptor-mediated study, FR 139317) to block ET-1 contractions has previously been shown in rat isolated trachea 16 and response exists in the airways, but a recent study found results similar to our own, in that the bronchohuman isolated bronchus. 17 In the present study, low constrictor response to ET-1 was significantly aughypoxic rat trachea.…”

Section: Discussionsupporting

confidence: 73%

“…to be mediated by activation of both ET A and ET B receptors. 13,16,17 Our preliminary experiments indicated that conMeasurement of contractile responses tractile responses to ET-1 were significantly attenuated Contractile responses were measured from rings of in isolated airways from rats exposed to chronic hytrachea in vertical organ baths (10 ml) at 37±0.5°C poxia. This may be due to an alteration in the ET in oxygenated (95% O 2 , 5% CO 2 ) Krebs-Henseleit receptor population in the airways since hypoxia has solution.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Chronic Hypoxia on Endothelin Receptor Subtype-mediated Responses in Rat Isolated Airways

Clayton

Nally

MacLean

et al. 1999

Pulmonary Pharmacology & Therapeutics

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of Chronic Hypoxia on Endothelin Receptor Subtype-mediated Responses in Rat Isolated Airways

Clayton

Nally

MacLean

et al. 1999

Pulmonary Pharmacology & Therapeutics

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“…These different types of cross talk include findings in which the ET-1-induced contraction is (1) not inhibited by separate ET A and ET B receptor blockade, as observed in guinea pig mesenteric vein, human bronchus, mouse trachea, rabbit pulmonary artery and jugular vein, and rat pulmonary arteriole and trachea 6,7,9,10,15,19,[24][25][26] (Fig. 2A); (2) inhibited by ET A but not ET B receptor blockade, as observed in mouse mesenteric vein, pig coronary artery, rabbit pulmonary arteriole, and rat mesenteric arteriole and trachea 2,12,16,18,21 (Figs. 2B-E); (3) inhibited by separate ET A and ET B receptor blockade, as observed in mouse renal efferent and rat renal afferent arteriole 13,28 (Fig.…”

Section: Functional Criteriamentioning

confidence: 86%

EndothelinA–EndothelinB Receptor Cross Talk in Endothelin-1–Induced Contraction of Smooth Muscle

Rapoport

Zuccarello²

2012

Journal of Cardiovascular Pharmacology

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The efficacy of selective endothelin (ET) receptor antagonists may be limited by a functional interaction between the ET(A) and ET(B) receptors. This interaction, also termed "cross talk", is characterized by the dependency of the inhibition of an ET-1 response due to antagonism of one ET receptor subtype upon concomitant antagonism of the other ET receptor subtype. Although a reduction in ET(A)-ET(B) receptor cross talk would presumably increase the efficacy of selective ET receptor antagonists, an approach that accomplishes this aim is largely absent due to a lack of mechanistic understanding. Toward this goal, we evaluated the characteristics and potential dependencies of cross talk in smooth muscle. Smooth muscle was adopted as an exemplar not only because cross talk is widely reported in this tissue type, thereby allowing numerous comparisons, but also significant controversy surrounds the use of selective versus nonselective ET receptor antagonists in ET-1-related pathophysiologies involving smooth muscle. Based on this evaluation, we suggest that ET(A)-ET(B) receptor cross talk is a dynamic process directed by either or both ET receptor subtypes and expressed to varying magnitudes depending on the ET-1 and selective ET receptor antagonist concentrations, tone due to intraluminal pressure/stretch, agonists acting at receptors other than the ET(A)/ET(B) receptors, and endothelial/epithelial function. It is speculated that ET(A)-ET(B) receptor cross talk occurs through signal transduction pathways along with changes at the receptor level. Pharmacologic intervention of the signaling pathways could increase the therapeutic efficacy of ET receptor antagonists.

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“…Numerous studies have shown that in rat aorta stimulation of α 1 -adrenoceptors (possibly α 1D -adrenoceptors; Villalobos-Molina and Ibarra 1996;Hussain and Marshall 1997;Ibarra et al 1997;Xu et al 1998), endothelin receptors (presumably ET A -receptors; Warner et al 1993;O'Donnell and Kay 1995) and prostanoid receptors (TP-receptors; Zhang et al 1996;Tosun et al 1997) causes pronounced vasoconstriction. It is generally believed that these receptors couple via G q/11 -protein to the phospholipase C (PLC)/inositoltrisphosphate (IP 3 )/diacylglycerol (DAG) system.…”

Section: Introductionmentioning

confidence: 99%

Inositolphosphate formation in thoracic and abdominal rat aorta following G q/11 -coupled receptor stimulation

Dhein

Giessler

Becker

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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Although thoracic and abdominal rat aorta are often used as a classical pharmacological preparation for the assessment of vascular drug effects, little is known on regional differences among these two parts of the aorta with regard to their reaction to Gq/11-coupled receptor activation. Thus, we determined, in rings from thoracic and abdominal aorta from 12-week-old male Wistar rats, the effects of noradrenaline (NA; 10(-8)-10(-4) M), endothelin-1 (ET-1; 10(-10)-10(-6) M) and the thromboxane A2 mimetic U 46619 (10(-8)-10(-5) M) on inositolphoshate (IP) formation (assessed as accumulation of total [3H]IPs in [3H]myoinositol prelabelled rings). NA, ET-1 and U 46619 concentration-dependently increased IP formation; maximum increases were, however, significantly more pronounced in thoracic than in abdominal aorta. Similarly, NA, ET-1 and U 46619 evoked significantly larger maximum contractions in thoracic than in abdominal aorta. NA-induced [3H]IP formation could be inhibited with BMY 7378 (10(-9)-10(-4) M) and with 5-methyl-urapidil (5-MU; 10(-9)-10(-5) M) both exhibiting biphasic concentration-inhibition curves. The pKi-values for BMY 7378 at the high affinity site were in thoracic aorta 8.93+/-0.28 (n=5), and in abdominal aorta 8.76+/-0.35 (n=4) and at the low affinity site 6.45+/-0.2 (thoracic aorta) and 6.55+/-0.27 (abdominal aorta). pKi-Values for 5-MU in thoracic aorta at the high affinity site were 8.25+/-0.34 (n=4), and at the low affinity site 6.61+/-0.39 . In abdominal aorta reliable pKi-values could not be calculated for 5-MU due to a low signal-to-noise ratio. On the other hand, in both preparations the ETA-receptor antagonist BQ-123 (10(-9)-10(-5) M) and the TP-receptor antagonist SQ 29548 (10(-9)-10(-5) M) inhibited ET-1- and U 46619-induced IP formation, respectively, with monophasic concentration-inhibition curves: pKi-values for BQ-123 were: 8.16+/-0.24 (thoracic aorta) and 8.10+/-0.35 (abdominal aorta) and for SQ 29548: 8.2+/-0.3 (thoracic aorta) and 8.5+/-0.3 (abdominal aorta). The amount of immunodetectable Gq/11-protein was similar in both tissues. We conclude that responses to NA, ET-1 and U 46619 (IP formation and contractile force) are larger in thoracic than in abdominal aorta. ET-1 effects on IP formation are mediated by ETA-receptors and U 46619 effects by TP-receptors. NA effects are mediated by alpha1D- and alpha1A-adrenoceptors; alpha1B-adrenoceptors seem to play a minor role.

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Effects of Endothelin Receptor Selective Antagonists, BQ-123 and BQ-788, on IRL 1620 and Endothelin-1 Responses of Airway and Vascular Preparations from Rats

Cited by 12 publications

References 0 publications

The Effect of Chronic Hypoxia on Endothelin Receptor Subtype-mediated Responses in Rat Isolated Airways

The Effect of Chronic Hypoxia on Endothelin Receptor Subtype-mediated Responses in Rat Isolated Airways

EndothelinA–EndothelinB Receptor Cross Talk in Endothelin-1–Induced Contraction of Smooth Muscle

Inositolphosphate formation in thoracic and abdominal rat aorta following G q/11 -coupled receptor stimulation

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