Endothelin: Receptor subtypes, signal transduction, regulation of ca2+ transients and contractility in rabbit ventricular myocardium

Endoh, Masao; Fujita, Shinji; Huang, Yang; Talukder, Milton; Maruya, Jun; Norota, Ikuo

doi:10.1016/s0024-3205(98)00094-0

Cited by 68 publications

(51 citation statements)

References 24 publications

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“…In fact, PLC␤3-deficient mice exhibit an almost complete loss of serotonin-or ␣-Me-5-HT-induced scratching. By contrast, the PLC␤3-deficient mutant mice respond normally to ET-1, SLIGRL-NH 2 (a protease-activated receptor 2 agonist) and U-46619 (a thromboxane A2 receptor agonist), despite the fact that the cognate receptors corresponding to these ligands also signal via G␣q-PLC␤ (22)(23)(24). Therefore, we conclude that G␣q-coupled pruritic compounds elicit an itch response through at least 2 different G␣q pathways: one is PLC␤3-dependent and the other is PLC␤3-independent.…”

Section: The Molecular Specificity Of G␣q-plc␤ Intracellular Signalinmentioning

confidence: 99%

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

Isowa

Park

Lee

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

391

437

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The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLC␤3-or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLC␤3 and the TRPV1 channel; 2) serotonin, or a selective agonist, ␣-methylserotonin (␣-Me-5-HT), requires the presence of PLC␤3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLC␤3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD ؉ neurons that represent Ϸ90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1 ؉ nociceptors led to a significant behavioral deficit for pruritogens, including ␣-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways.itch ͉ PLCb3 ͉ scratching

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Section: The Molecular Specificity Of G␣q-plc␤ Intracellular Signalinmentioning

confidence: 99%

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

Isowa

Park

Lee

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

391

437

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“…ET isopeptides induce a pronounced positive inotropic effect associated with stimulation of phosphoinositide hydrolysis (71) via predominant activation of ET A receptors (73) in mammalian ventricular myocardium of most species (70,74,76). The positive inotropic effect of ET isopeptides shows a wide range of species-dependent variation.…”

Section: -4 Etmentioning

confidence: 99%

“…The most pronounced positive inotropic effect is observed in rabbit ventricular myocardium among the species examined; and ET-1, ET-2, and ET-3 exert the effect with an identical efficacy and potency (70). While the positive inotropic effect of ET-3 (73), and ET-1 at lower concentrations (<10 −8 M) (72), is susceptible to ET A -receptor antagonists, the ET A -receptor antagonists are unable to shift the main portion of the concentration-response curve for ET-1 in rabbit papillary muscle (72,76,81). The potent ET A -receptor antagonist TAK-044 can inhibit the positive inotropic effect of ET-1 in the rabbit, but a concentration one hundred times higher than that which inhibits the ET-3-induced response is required (83).…”

Section: -4 Etmentioning

confidence: 99%

Signal Transduction and Ca2+ Signaling in Intact Myocardium

Endoh

2006

J Pharmacol Sci

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Abstract. The experimental procedures to simultaneously detect contractile activity and Ca 2+transients by means of the Ca 2+ sensitive bioluminescent protein aequorin in multicellular preparations, and the fluorescent dye indo-1 in single myocytes, provide powerful tools to differentiate the regulatory mechanisms of intrinsic and external inotropic interventions in intact cardiac muscle. The regulatory process of cardiac excitation-contraction coupling is classified into three categories; upstream (Ca 2+ mobilization), central (Ca 2+ binding to troponin C), and / or downstream (thin filament regulation of troponin C property or crossbridge cycling and crossbridge cycling activity itself) mechanisms. While a marked increase in contractile activity by the Frank-Starling mechanism is associated with only a small alteration in Ca 2+ transients (downstream mechanism), the force-frequency relationship is primarily due to a frequencydependent increase of Ca 2+ transients (upstream mechanism) in mammalian ventricular myocardium. The characteristics of regulation induced by β-and α-adrenoceptor stimulation are very different between the two mechanisms: the former is associated with a pronounced facilitation of an upstream mechanism, whereas the latter is primarily due to modulation of central and / or downstream mechanisms. α-Adrenoceptor-mediated contractile regulation is mimicked by endothelin ET A -and angiotensin II AT 1 -receptor stimulation. Acidosis markedly suppresses the regulation induced by Ca 2+ mobilizers, but certain Ca 2+ sensitizers are able to induce the positive inotropic effect with central and / or downstream mechanisms even under pathophysiological conditions.

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“…sensitivity induced by ET-1 is due to an intracellular alkalinization and / or an increase in phosphorylation of myofilaments (10,11), but the signaling process responsible for the Ca 2+ sensitization has not been fully clarified.…”

Section: +mentioning

confidence: 99%

Wortmannin Inhibits the Increase in Myofilament Ca2+ Sensitivity Induced by Cross-Talk of Endothelin-1 With Norepinephrine in Canine Ventricular Myocardium

et al. 2009

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Abstract. Endothelin-1 (ET-1) modulates cardiac contractility by cross-talk with norepinephrine (NE) in canine ventricular myocardium. The present experiments were performed to investigate the influence of wortmannin that has inhibitory action on phosphatidylinositol 3-kinase (PI3-K) (IC 50 = 3 nM) and myosin light chain kinase (MLCK) (IC 50 = 200 nM) on Ca 2+ signaling and the inotropic effects of ET-1 induced by cross-talk with NE. Experiments were carried out in isolated canine ventricular trabeculae and indo-1 / AM-loaded single ventricular cardiomyocytes. ET-1 alone elicited a transient small negative inotropic effect (NIE). In the presence of NE at low (1 -10 nM) and high (100 nM) concentrations, ET-1 induced a long-lasting positive inotropic effect (PIE) or a marked sustained NIE, respectively. Wortmannin up to 300 nM did not affect the contractility; and at 1 μM and higher, it decreased the basal contraction without suppressing Ca 2+ transients. Wortmannin (1 μM) inhibited the long-lasting PIE of ET-1 without affecting the ET-1-induced increase in Ca 2+ transients. Wortmannin at the same concentration did not affect the ET-1-induced transient and sustained NIE and the PIE mediated by β-adrenoceptor stimulation. These results imply that wortmannin exerts selective inhibitory action on the increase in myofilament Ca 2+ sensitivity induced by cross-talk of ET-1 with NE probably through an inhibition of MLCK in canine ventricular myocardium.

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Endothelin: Receptor subtypes, signal transduction, regulation of ca2+ transients and contractility in rabbit ventricular myocardium

Cited by 68 publications

References 24 publications

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

Signal Transduction and Ca2+ Signaling in Intact Myocardium

Wortmannin Inhibits the Increase in Myofilament Ca2+ Sensitivity Induced by Cross-Talk of Endothelin-1 With Norepinephrine in Canine Ventricular Myocardium

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