Regional modulation of cyclic nucleotides by endothelin‐1 in rat pulmonary arteries: direct activation of G<sub>i</sub>2‐protein in the main pulmonary artery

Mullaney, Ian; Vaughan, D.; MacLean, Margaret R.

doi:10.1038/sj.bjp.0703153

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…3). In general support of this suggestion are the observations that (1) ET A and ET B receptors can couple to pathways predicted to either increase or decrease ET-1-induced contraction [66][67][68][69] and (2) ET-1 differentially activates the various pathways coupled to the ET A and ET B receptors depending on the ET-1 concentration. 70 It is of interest to speculate that the enhanced ET-1 contraction that occurs after ET A or ET B receptor blockade in the absence of the endothelium 7,20,22,24,37,65,71 may be due to inhibition of negative regulatory pathways.…”

Section: Mechanism Signaling Pathwaysmentioning

confidence: 69%

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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Section: Mechanism Signaling Pathwaysmentioning

confidence: 69%

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

Rapoport

Zuccarello²

2012

Journal of Cardiovascular Pharmacology

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“…Functional data also demonstrated that ET-1-induced vasoconstriction in intraparenchymal arteries is mediated by both the ET A and the ET B receptor subtypes (McLean et al 1994; Higashi et al 1997). ET A and ET B receptors are known to be differentially coupled to G-proteins, and in small pulmonary arteries, levels of the cyclic nucleotides cAMP and cGMP were shown to be differentially regulated by either ET A or ET B receptor stimulation (Mullaney et al 2000). In the rabbit pulmonary circulation, vasoconstriction induced by ET-1 shifted from the ET A to the ET B receptor subtype after preconstriction (Schmeck et al 1999), suggesting that the contribution of ET B receptors to the vasoconstriction elicited by ET-1 depends on vascular tone.…”

Section: Discussionmentioning

confidence: 99%

Muscular ET_BReceptors Develop Postnatally and Are Differentially Distributed in Specific Segments of the Rat Vasculature

Wendel

Kummer

Knels

et al. 2005

J Histochem Cytochem.

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S U M M A R YThe endothelin/endothelin-receptor system is a key player in the regulation of vascular tone in mammals. We raised and characterized an antiserum against rat ET B receptor and investigated the distribution of ET B receptors in different vascular beds during postnatal development (day 0 through day 28) and in the adult rat. We report the tissuespecific and age-dependent presence of vasoconstrictor ET B receptors. At the time of birth, vascular smooth muscle cells from all tissues examined did not exhibit ET B receptor immunoreactivity. The occurrence of ET B receptor immunoreactivity in the postnatal development was time dependent and started in small coronary and meningeal arteries at day 5, followed by small mesenteric arteries as well as brachial artery and vein at day 14. At day 21, ET B receptors were present in the media of muscular segments of pulmonary artery, large coronary arteries, and intracerebral arterioles. At day 28, ET B receptor immunoreactivity was evident in interlobular renal arteries, vas afferens, and efferens. Large renal arteries, mesenteric artery, and elastic segments of pulmonary arteries, as well as coronary and mesenteric veins, did not exhibit ET B receptor immunoreactivity. These data demonstrate the age-dependent and tissue-specific presence of ET B receptors, mainly on arterial smooth muscle cells in the vascular system of the rat. E ndothelin -1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide (Yanagisawa et al. 1989). It takes part in the regulation of vascular tone after birth (for review see Perreault and Coceani 2003) and is implicated in the pathophysiology of cardiovascular, renal, and pulmonary diseases (Saito et al. 1990;Watanabe et al. 1990;Larriviere and Lebel 2003;Michel et al. 2003).ET-1 exerts its biological effects through two distinct ET-receptor subtypes, ET A and ET B . ET A receptors on smooth muscle cells exclusively mediate vasoconstriction, whereas ET B receptors can mediate both vasodilation as well as vasoconstriction, depending on their location on endothelial cells and vascular smooth muscle, respectively. While the role of the ET A receptor subtype in mediating vasoconstriction is beyond debate, the existence of ET B receptors on vascular smooth muscle cells in distinct vascular beds is still controversial, and systematic histological investigations on the distribution pattern of vascular ET receptors are missing. Recently, colocalization of ET A and ET B receptors on arterial smooth muscle cells in the coronary circulation (Wendel-Wellner et al. 2002) and small pulmonary arteries of adult rats were demonstrated (Soma et al. 1999).Pharmacological studies aimed at defining the role of vasoconstrictor ET B receptors are highly controversial, and studies from different groups lead to contradictory results even for identical organ systems (Takase et al.

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Endothelin-Induced Changes of Secondary Messengers in Cultured Corneal Endothelial Cells

Hong

Lin

et al. 2001

Journal of Ocular Pharmacology and Therapeutics

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The effect of endothelins on corneal endothelial cells is not well understood. We have investigated the effects of endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3) on bovine corneal endothelial cellular proliferation and the secondary messenger changes in cells in the presence of ET-1. It was found that the 3H-thymidine uptake was enhanced by ET-1 significantly, whereas ET-2 and ET-3 had no effect. ET-1 remarkably affects the increase of corneal endothelial cells on 3H-thymidine, 3H-leucine, and 3H-uridine uptakes in a dose-dependent manner. The 50% effective concentrations (EC50) for ET-1, as measured by 3H-thymidine uptake, 3H-uridine uptake, and 3H-leucine uptake were 10(-8.78) M, 10(-8.53) M and 10(-8.04) M, respectively. It was found that endothelin-1 increased intracellular calcium concentration by using the method of preloading with Fura-2-AM and assaying with spectrophotometry. The cellular IP1, IP2, and IP3 were also stimulated in the presence of ET-1. Moreover, ET-1 enhanced the basal cellular cAMP and cGMP concentrations in corneal endothelial cells in a dose-dependent manner. Immunofluorescent staining revealed that ET-1 increased the fibronectin protein concentration and changed protein distribution in corneal endothelial cells. These findings indicate that endothelin-1 increases in cell proliferation and biological changes may be involved in changing intracellular calcium mobility, increasing intracellular phosphoinositides, enhancing intracellular cGMP and cAMP accumulation, and fibronectin protein synthesis.

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Regional modulation of cyclic nucleotides by endothelin‐1 in rat pulmonary arteries: direct activation of G_i2‐protein in the main pulmonary artery

Cited by 4 publications

References 48 publications

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

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

Muscular ET_BReceptors Develop Postnatally and Are Differentially Distributed in Specific Segments of the Rat Vasculature

Endothelin-Induced Changes of Secondary Messengers in Cultured Corneal Endothelial Cells

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Regional modulation of cyclic nucleotides by endothelin‐1 in rat pulmonary arteries: direct activation of Gi2‐protein in the main pulmonary artery

Cited by 4 publications

References 48 publications

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

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

Muscular ETBReceptors Develop Postnatally and Are Differentially Distributed in Specific Segments of the Rat Vasculature

Endothelin-Induced Changes of Secondary Messengers in Cultured Corneal Endothelial Cells

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Regional modulation of cyclic nucleotides by endothelin‐1 in rat pulmonary arteries: direct activation of G_i2‐protein in the main pulmonary artery

Muscular ET_BReceptors Develop Postnatally and Are Differentially Distributed in Specific Segments of the Rat Vasculature