Dual role of endothelin-1 via ET<sub>A</sub> and ET<sub>B</sub> receptors  in regulation of cardiac contractile function in mice

Piuhola, Jarkko; Mäkinen, Markus J.; Szokodi, István; Ruskoaho, Heikki

doi:10.1152/ajpheart.00480.2002

Cited by 26 publications

(35 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8), which is an indication that the activation of ET B receptors that results in an inhibitory action is partially responsible for the absence of PIE of ET-1 in the canine ventricular myocardium, which is consistent with the previous findings in I Ca(L) current in rabbit ventricular cardio-myocytes (24) and mouse heart (35). ET-1 may activate receptor subtypes that trigger both positive and negative inotropic responses, the latter being more susceptible to the antagonistic action of BQ-788.…”

Section: Sustained Pie Of Et-1 Under Et B -Receptor Blockade By Bq-788supporting

confidence: 92%

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

et al. 2005

View full text Add to dashboard Cite

Abstract. In canine ventricular myocardium, endothelin-1 (ET-1) alone induced only a weak transient negative inotropic effect (NIE). However, ET-1 induced a marked sustained positive inotropic effect (PIE) subsequent to a transient NIE in the presence of norepinephrine (NE) at low concentrations (0.1 -1 nM) and elicited a pronounced sustained NIE in the presence of NE at high concentrations (around 100 nM). Thus, the extent of b-adrenoceptor stimulation induced by NE played a crucial role in determining the characteristics of the inotropic effects of ET-1. The characteristics of ET receptor subtypes involved in contractile regulation and Ca 2+ signaling induced by ET-1 were determined. The ET-1-induced transient NIE and decrease in Ca transients were abolished by the selective ET A -receptor antagonist FR319317, but not by the selective ET B -receptor antagonist BQ-788. The sustained PIE and the increase in Ca 2+ transients induced by ET-1 were abolished by FR319317, but not inhibited by BQ-788. In contrast, the sustained NIE of ET-1 was abolished by the non-selective ET antagonist TAK-044, markedly attenuated by FR319317, and partially inhibited by BQ-788. ET-1 alone elicited a PIE in the presence of BQ-788, which indicates that the activation of ET B -receptors counteracts the development of the PIE of ET-1. The current findings indicate that both ET A and ET B receptors are involved in the regulation of Ca 2+ signaling and contractility in canine ventricular myocardium.

show abstract

Section: Sustained Pie Of Et-1 Under Et B -Receptor Blockade By Bq-788supporting

confidence: 92%

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Several genes displayed a remarkably high expression level in all four heart chambers, suggesting that they may play a prominent role in heart physiology. Indeed, the endothelin ET A receptor was the most abundantly expressed overall and is well known for modulating cardiac contractile function (Piuhola et al, 2003). Quite surprisingly, little information is available concerning the physiological cardiac function of many of the most abundantly expressed receptors: the anaphylatoxin C5a, prostanoid EP 1 , sphingolipid S 1 P 3 , frizzled FZD4, chemokine CMKOR1, and lung seven-transmembrane receptors Lustr1 and Lustr2.…”

Section: Resultsmentioning

confidence: 99%

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Moore-Morris¹,

Varrault²,

Mangoni³

et al. 2009

Mol Pharmacol

View full text Add to dashboard Cite

Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functions represents an important issue for the development of new drugs. Indeed, highly targeted receptors represent only a small percentage of known GPCRs. Here, we quantified the expression of 395 endoGPCRs (all GPCRs excluding taste and odorant receptors) in male mouse right and left atria and ventricles by using high-throughput real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and focused on the 135 most highly expressed transcripts. No cardiac functional data are available for almost half of these receptors; therefore, linking GPCR expression patterns to cardiac function has allowed us to provide new insights into the possible function of some of these receptors. Indeed, ventricles and atria are both contractile; however, the latter, and especially the right atrium, are central to the generation and regulation of cardiac rhythm. Accordingly, the right atrium exhibited the most specific signature, whereas the majority of GPCRs found in ventricles were evenly expressed in both the right and left chambers. RT-PCR data were confirmed at the protein level for six selected transcripts. Furthermore, we provide new data showing that, as suggested by our repertoire, the metabotropic glutamate receptor 1b is expressed and is functional in ventricular cardiac myocytes. This is the first report describing GPCRs in the four cardiac chambers and may assist in the identification of therapeutic targets.The four cardiac chambers display morphological and functional differences. They can be distinguished on the basis of contractile properties, rhythm generation, and response to neurohumoral stimulation (Brown et al., 1991;Barth et al., 2005;Narolska et al., 2005). Contractile activity of the heart ensures that blood flow is adapted to the needs of the organism. Left ventricular performance depends on the chamber's capacity to fill up (diastolic property) and to empty (systolic property), and these properties are altered in pathological conditions, the final consequence being heart failure. To trigger the contractile activity, cardiac automaticity is generated by a set of specialized pacemaker cells forming the sinoatrial node (SAN) (Mangoni and Nargeot, 2008). Compared with myocytes of the working myocardium, pacemaker SAN cells are devoted to the generation of an electrical oscillation rather than having a contractile activity. At the molecular level, heart chamber heterogeneity is reflected by the expression patterns of different sets of genes such as transcription factors (Tabibiazar et al., 2003) and ion channels (Marionneau et al., 2005). The heart expresses GPCRs (Regard et al.,

show abstract

“…Results in mouse have indicated opposite roles for ET A and ET B -receptors in the regulation of contractile force (52). ET Areceptor activation accounts for ET-1-mediated enhancement of contractile force during elevated load, whereas ET B receptor activation has an inhibitory action on contractile function (52).…”

Section: Discussionmentioning

confidence: 99%

Synergistic activation of salmon cardiac function by endothelin and β-adrenergic stimulation

Vierimaa

Ronkainen²,

Ruskoaho³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

The aim was to find out the effects of endothelin-1 (ET-1) in salmon (Salmo salar) cardiac contractile and endocrine function and its possible interaction with beta-adrenergic regulation. We found that ET-1 has a positive inotropic effect in salmon heart. ET-1 (30 nM) increased the contraction amplitude 17+/-4.7% compared with the basal level. beta-Adrenergic activation (isoprenaline, 100 nM) increased contraction amplitude 30+/-13.1%, but it did not affect the contractile response to ET-1. ET-1 (10 nM) stimulated the secretion of salmon cardiac natriuretic peptide (sCP) from isolated salmon ventricle (3.3+/-0.14-fold compared with control) but did not have any effect on ventricular sCP mRNA. Isoprenaline alone (0.1-1,000 nM) did not stimulate sCP release, but ET-1 (10 nM) together with isoprenaline (0.1 nM) caused a significantly greater increase of sCP release than ET-1 alone (5.4+/-0.07 vs. 3.3+/-0.14 times increase compared with control). The effects on the contractile and secretory function could be inhibited by a selective ETA-receptor antagonist BQ-610 (1 microM), whereas ETB-receptor blockage (by 100 nM BQ-788) enhanced the secretory response. Thus ET-1 is a phylogenetically conserved regulator of cardiac function, which has synergistic action with beta-adrenergic stimulation. The modulatory effects of ET-1 may therefore be especially important in situations with high beta-adrenergic tone.

show abstract

Dual role of endothelin-1 via ET_A and ET_B receptors in regulation of cardiac contractile function in mice

Cited by 26 publications

References 37 publications

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Synergistic activation of salmon cardiac function by endothelin and β-adrenergic stimulation

Contact Info

Product

Resources

About

Dual role of endothelin-1 via ETA and ETB receptors in regulation of cardiac contractile function in mice

Cited by 26 publications

References 37 publications

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Synergistic activation of salmon cardiac function by endothelin and β-adrenergic stimulation

Contact Info

Product

Resources

About

Dual role of endothelin-1 via ET_A and ET_B receptors in regulation of cardiac contractile function in mice