Abstract
Endothelin is one of the most potent vasoconstrictors known. It plays an important role in the regulation of vascular tone and in the development of many cardiovascular diseases. This study focuses on the receptor types and the Ca2+ mobilization responsible for endothelin-1 (ET-1) contraction in de-endothelialized pig coronary artery rings. ET-1 contracted the artery rings with an EC50 = 6.5 ± 1 nM and a maximum contraction which was 98.6 ± 9% of the contraction produced by 60 mM KC1. BQ123 (5 μM), an ETA antagonist, reversed 78 ± 3% of the ET-1 contraction (50 nM). IRL1620, a selective ETB agonist, produced 23 ± 3% of the total ET-1 contraction with an EC50= 12.7 ± 2 nM. More than 85% of the contraction due to 100 nM IRL 1620 was inhibited by 200 nMBQ788, an ETB antagonist. Therefore, approximately 80% of the ET-1 contraction in this artery occurred via ETA receptors, and the other 20% was mediated by ETB receptors. To assess the Ca2+ pools utilized during the ET-1 response, ET-1 contraction was also examined in medium containing an L-type Ca2+ channel blocker nitrendipine, and in Ca2+ free medium containing 0.2 mM EGTA. In Ca2+ containing medium the contraction elicited by ET-1 was 98.6 ± 9% of the KC1 contraction, however, in the presence 10 µM nitrendipine the ET-1 induced contraction was 54 ± 7% of the KC1 contraction, and in Ca2+-free medium it was 13 ± 2%. Similarly, the IRL 1620 contractions in Ca2+ containing medium, in the presence of nitrendipine and in Ca2+-free medium were 22.4 ± 3%, 12 ± 3% and 11 ± 2% of the KC1 response respectively. Thus, both ETA and ETB contractions utilize extracellular Ca2+ pools via L-type Ca2+ channels and other undefined route(s), as well as intracellular Ca2+ pools. In the pig coronary artery smooth muscle, ET-1 contractions occur predominantly via ETA receptors, with ETB receptors using similar Ca2+ mobilization pathways, but the ETB receptors appear to use the intracellular Ca2+ stores to a greater extent. (Mol Cell Biochem 176: 29–33, 1997)
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Abbreviations
- ET-1:
-
endothelin-1
- EGTA:
-
ethyl glycol-bis(β-aminoethyl ether)-N,N,N’,N’-tetraacetic acid
References
Van Renterghem C, Vigne P, Barhanin J, Schmid-Alliana A, Freiin C, Lazdunski M: Molecular mechanism of action of the vasoconstrictor peptide endothelin. Biochem and Biophys Res Comm 157: 977–985, 1988
Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K: The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Nat Acad Sci USA 86: 2863–2867, 1989
White DG, Cannon TR, Garratt H, Mundin JW, Summer MJ, Watts IS: Endothelin ETA and ETB receptors mediate vascular smooth-muscle contraction. J Cardiovasc Pharmacol 22: S144–S148, 1993
Bacon CR, Davenport AP: Endothelin receptors in human coronary artery and aorta. Br J Pharmacol 117: 986–992, 1996
Tonnessen T, Naess PA, Kirkeboen KA, Offstad J, Ilebekk A, Christensen G: Endothelin is released from the porcine coronary
Moreland S, McMullen D, Abboa-Offei B, Seymour A: Evidence for a differential location of vasoconstrictor endothelin receptors in the vasculature. Brit Jour Pharmacol 112: 704–708, 1994
Pollock DM, Opgenorth TJ: ETA receptor-mediated responses to endothelin-1 and big endothelin-1 in the rat kidney. Brit Jour Pharmacol 111: 729–732, 1994
Godfraind T: Evidence for heterogeneity of endothelin receptor distribution in human coronary artery. Brit Jour Pharmacol 110: 1201–1205, 1993
Takigawa M, Sakurai T, Kasuya Y, Abe Y, Masaki T, Goto K: Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. European Jour Biochem 228: 102–108, 1995
Goto K, Kasuya Y, Matsuki N, Takuwa Y, Kurihara H, Ishikawa T, Yanagisawa M, Masaki T: Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle. Proc Nat Acad Sci USA 86: 3915–3918, 1989
Wagner-Mann C, Bowman L, Sturek M: Primary action of endothelin on Ca release in bovine coronary artery smooth muscle cells. Am J Physiol 260: C763–C770, 1991
Grover AK, Fomin VP, Samson SE: Angiotensin II contractions in coronary artery: Nature of receptors and calcium pools. Mol Cell Biochem 135:11–19, 1994
Clarke JG, Benjamin N, Larkin SW, Webb DJ, Davies GJ, Maseri A: Endothelin is a potent long-lasting vasoconstrictor in men. Am J Physiol 257: H2033–H2033, 1989
Takai M, Umemura I, Yamasaki K, Watakabe T, Fujitani Y, Oda K, Urade Y, Inui T, Yamamura T, Okada T: A potent and specific agonist, Suc-[Glu9,Alal 1, 15]-endothelin-1(8-21), IRL 1620, for the ETB receptor. Biochem Biophys Res Comm 184: 953–959, 1992
Ihara M, Noguchi K, Saeki T, Fukuroda T, Tsuchida S, Kimura S, Ishikawa K, Nishikibe M, Yano M: Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci 50: 247–255, 1992
Ishikawa K, Ihara M, Noguchi K, Mase T, Mino N, Saeki T, Fukuroda T, Fukami T, Ozaki S, Nagase T et al.: Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Acad Sci USA 91: 4892–4896, 1994
Maguire JJ, Kuc RE, O’Reilly G, Davenport AP: Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro. Brit Jour Pharmacol 113: 49–54, 1994
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Elmoselhi, A.B., Grover, A.K. (1997). Endothelin contraction in pig coronary artery: Receptor types and Ca2+-mobilization. In: Singal, P.K., Panagia, V., Pierce, G.N. (eds) The Cellular Basis of Cardiovascular Function in Health and Disease. Developments in Molecular and Cellular Biochemistry, vol 22. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5765-4_4
Download citation
DOI: https://doi.org/10.1007/978-1-4615-5765-4_4
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7642-2
Online ISBN: 978-1-4615-5765-4
eBook Packages: Springer Book Archive