Identification of endothelin receptors in various regions of rat brain

doi:10.1016/0143-4179(90)90062-4

Neuropeptides

Volume 16, Issue 4, August 1990, Pages 195-199

https://doi.org/10.1016/0143-4179(90)90062-4 Get rights and content

Abstract

Endothelins (ET) are a family of 21 amino acid peptides which carry a high degree of hemology. ET-1, originally isolated from porcine endothelium in culture, is an unusually potent vasoconstrictor. Recent studies indicated the presence of ET-1 and ET-3 in the CNS, and autoradiographic evidence supported the presence of specific ET-1 binding sites. The present study aimed to raise evidence in support for the presence of ET-1 and ET-3 receptors in the rat CNS, to establish their spatial distribution, and gain insight on the molecular species which could be associated to ET-1 and ET-3 binding. The data support the presence of specific binding sites for ET-1 and ET-3 and a heterogeneous distribution of these sites in the CNS. The highest densities were found in the cerebellum (> 2200 fmol-mg protein) and the lowest in the cerebral cortex (500 fmol/mg protein). Our data also suggest that ET-1 and ET-3 labelled two different proteins of 45 Kd and 37 Kd molecular weight, but no evidence for separate ET-1 and ET-3 receptors could be noted. These data provide further evidence in support for the possible role of ET-1 and ET-3 in neuromodulation/neurotransmisson in the CNS.

References (17)

O. Shinmi et al.
Presence of endothelin-1 in porcine spinal cord: isolation and sequence determination
Biochem. Biophys. Res. Commun.
(1989)
A.L. Siren et al.
Hemodynamic effects of endothelin after systemic and central nervous system administration in the conscious rat
Neuropeptides
(1989)
H. Watanabe et al.
Two distinct types of endothelin receptors are present on chick cardiac membranes
Biochem. Biophys. Res. Commun.
(1989)
Y. Masuda et al.
Two different forms of endothelin receptors in rat lung
FEBS Lett.
(1989)
M. Yanagisawa et al.
A novel potent vasoconstrictor peptide produced by vascular endothelial cells
Nature
(1988)
D. Ezra et al.
Lethal ischemia due to intracoronary endothelin in the pig
Am. J. Physiol.
(1989)
Y. Kloog et al.
Saroyatoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain
Science
(1988)
T. Yoshizawa et al.
Endothelin: a novel peptide in the posterior pituitary system
Science
(1990)

There are more references available in the full text version of this article.

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Endothelin-1_1–31 (ET-1_1–31) is a novel member of the endothelin family, which comprises 31 amino acids and derived from the selective hydrolysis of big ET-1 by chymase. Although ET-1_1–31 has been reported to be involved in biological effects via direct or indirect (converting to ET-1_1–21) mechanisms, the cardiovascular effects of central ET-1_1–31 are not fully identified. The present study was designed to comparatively investigate the cardiovascular effects of intracerebroventricular (icv) application of ET-1_1–31 or ET-1_1–21 in anesthetized rats. Injection (icv) of ET-1_1–31 (500 pmol) produced a biphasic blood pressure response: an initial increase (from 118 ± 8 to 138 ± 14 mmHg, P < 0.05) followed by a sustained decrease in BP (from 118 ± 8 to 58 ± 9 mmHg, P < 0.05), which was very similar to BP response to icv injection of big ET-1 (500 pmol) or ET-1_1–21 (25 pmol)_. The cardiovascular effects of icv injection of ET-1_1–31 or ET-1_1–21 were completely antagonized by ET_A receptor antagonist BQ123 but not ET_B receptor antagonist BQ788. Furthermore, pretreatment with ET converting enzyme inhibitor phosphoramidon (10 nmol) abolished the cardiovascular effects evoked by icv injection of ET-1_1–31 or big ET-1. In conclusion, the current data showed that central ET-1_1–31 produced the similar cardiovascular effects as those of central ET-1_1–21, and suggesting that the central cardiovascular effects of ET-1_1–31 resulted from it converting to ET-1_1–21 and then activating ET_A receptors.
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B103 neuroblastoma cells predominantly express endothelin ET<inf>B</inf> receptor; effects of extracellular Ca<sup>2+</sup> influx on endothelin-1-induced mitogenesis
2001, European Journal of Pharmacology
We sought to examine the effects of endothelin-1 on the intracellular free Ca²⁺ concentration ([Ca²⁺]_i) and mitogenic response in the neuroblastoma cell line, B103 (B103 cells). The results obtained from an [¹²⁵I] endothelin-1 binding assay demonstrated that B103 cells express the endothelin receptor. The B_max and K_d values for [¹²⁵I]endothelin-1 binding were 70±36 fmol/mg protein and 52±13 pM, respectively. Endothelin-1 failed to stimulate cAMP formation, but it did inhibit forskolin-induced cAMP formation. Endothelin-1 also stimulated the accumulation of [³H]inositol phosphates. These results indicate that the endothelin receptor in B103 cells couples with G_i and G_q but not with G_s. Monitoring of [Ca²⁺]_i showed that endothelin-1 evoked a transient increase in [Ca²⁺]_i; this remained even in the absence of extracellular Ca²⁺. However, no sustained, endothelin-1-induced increase in [Ca²⁺]_i due to extracellular Ca²⁺ influx was detected. The endothelin B receptor-selective antagonist, 2,6-Dimethylpiperidinecarbonyl-γ-Methyl-Leu-N_in-[Methoxycarbonyl]-d-Trp-d-Nle (BQ 788), abolished the endothelin-1-induced increase in [Ca²⁺]_i, while the endothelin ET_A receptor-selective antagonist, cyclo-d-Asp-Pro-d-Val-Leu-d-Trp (BQ 123), failed to inhibit it. These results indicate that B103 cells express endothelin ET_B receptor or an endothelin ET_B-like receptor predominantly and have no Ca²⁺ channels activated by endothelin-1. Endothelin-1 activated mitogen-activated protein kinase in B103 cells. However, based on the data for 3-(4,5-dimethy-2-thiazolyl)-2,5-diphenyl tetrazolium bromide, [³H]thymidine incorporation, and apoptosis screening assays, endothelin-1 induces neither mitogenesis nor apoptosis. These results suggest that endothelin-1 has no role in the mitogenic response in B103 cells, and this is consistent with the notion that an endothelin-1-induced sustained increase in [Ca²⁺]_i plays a role in endothelin-1-induced cell proliferation.
Endothelin receptor antagonists in congestive heart failure: A new therapeutic principle for the future?
2001, Journal of the American College of Cardiology
Congestive heart failure (CHF) is characterized by impaired left ventricular function, increased peripheral and pulmonary vascular resistance and reduced exercise tolerance and dyspnea. Thus, mediators involved in the control of myocardial function and vascular tone may be involved in its pathophysiology. The family of endothelins (ET) consists of four closely related peptides, ET-1, ET-2, ET-3 and ET-4, which cause vasoconstriction, cell proliferation and myocardial effects through activation of ET_Areceptors. In contrast, endothelial ET_Breceptors mediate vasodilation via release of nitric oxide and prostacyclin. In addition, ET_Breceptors in the lung are a major pathway for the clearance of ET-1 from plasma. Thus, infusion of an ET_A-receptor antagonist into the brachial artery in healthy humans leads to vasodilation, whereas infusion of an ET_B-receptor antagonist causes vasoconstriction. Endothelin-1 plasma levels are elevated in CHF and correlate both with hemodynamic severity and symptoms. Plasma levels of ET-1 and its precursor, big ET-1, are strong independent predictors of death after myocardial infarction as well as in CHF. Endothelin-1 contributes to increased systemic and pulmonary vascular resistance, vascular dysfunction, myocardial ischemia and renal impairment in CHF. Selective ET_A, as well as combined ET_A/B-receptor antagonists, have been studied in patients with CHF, and their use has shown impressive hemodynamic improvement (i.e., reduced peripheral vascular and pulmonary resistance as well as increased cardiac output). These results indicate that ET-receptor antagonists, indeed, have a potential to improve hemodynamics, symptoms and, potentially, prognosis in patients with CHF, which still carries a high mortality.
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2000, Handbook of Chemical Neuroanatomy
Endothelin (ET) was originally identified as a vasoactive peptide synthesized in vascular endothelial cells and Atrial Natriuretic Peptide (ANP) as a hormone produced and released by the heart. Both ET and ANP were later found in mammalian brain as part of more complex systems with a plurality of active peptides and their receptors. Together with Angiotensin II (Ang II) ET and ANP belong to the group of physiologically related brain-vascular peptide hormones contributing to the central regulation of autonomic and hormone systems and to the regulation of cerebral blood flow, limbic system physiology, cognition and development. This chapter discusses ET and ANP, with a brief mention of some of the most important interactions of these peptides with Ang II. The chapter focuses on the characterization, distribution, regulation of ET and ANP receptors, and on the consequences of their stimulation.

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View full text

Identification of endothelin receptors in various regions of rat brain

Abstract

Biochem. Biophys. Res. Commun.

Neuropeptides

Biochem. Biophys. Res. Commun.

FEBS Lett.

A novel potent vasoconstrictor peptide produced by vascular endothelial cells

Nature

Lethal ischemia due to intracoronary endothelin in the pig

Am. J. Physiol.

Saroyatoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain

Science

Endothelin: a novel peptide in the posterior pituitary system

Science