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. 1995 Jul;115(5):840–844. doi: 10.1111/j.1476-5381.1995.tb15009.x

Evidence for ETA and ETB receptors in rat skin and an investigation of their function in the cutaneous microvasculature.

E Lawrence 1, L Siney 1, P Wilsoncroft 1, G A Knock 1, G Terenghi 1, J M Polak 1, S D Brain 1
PMCID: PMC1908517  PMID: 8548185

Abstract

1. The relative contribution of ETA and ETB receptors in the response of rat skin to endothelins was investigated by use of the selective ETB agonist IRL-1620 and the selective ETA antagonist BQ-123. 2. Binding data suggest the presence of ETA and ETB receptors as preincubation with [Ala3,11,18Nle7]-endothelin-1 reduced ET-1 binding by approximately 40%. 3. Intradermal injection of endothelin-1 (ET-1, 1-10 pmol/site) and ET-3 (3-100 pmol/site) induced a dose-dependent decrease in local blood flow assessed by 133Xe clearance at test sites in rat skin. 4. The endothelin analogue [Ala3,11,18Nle7]-ET-1 (30-1000 pmol/site) induced significant vasoconstriction (P < 0.05) at the highest doses used and the selective ETB receptor agonist, IRL-1620 [Suc[Glu9,Ala11,15] endothelin (8-21)], (0.01-100 pmol/site) acted in a potent manner to induce a significant (P < 0.01) dose-dependent decrease in 133Xe clearance. 5. Co-injection with the selective ETA receptor antagonist, BQ-123 (1 nmol/site), completely abolished the vasoconstriction to ET-1 and partially to ET-3, but had no effect on IRL-1620-induced vasoconstriction. In addition, IRL-1620 responses were not altered at sites treated with submaximal doses of a nitric oxide synthase inhibitor or a prostaglandin synthase inhibitor. 6. ET-1 and IRL-1620 (100 fmol-1 pmol/site) did not induce oedema formation as measured by [125I]-albumin accumulation in the presence or absence of the vasodilator, calcitonin gene-related peptide (CGRP).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Arai H., Hori S., Aramori I., Ohkubo H., Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature. 1990 Dec 20;348(6303):730–732. doi: 10.1038/348730a0. [DOI] [PubMed] [Google Scholar]
  2. Borić M. P., Donoso V., Fournier A., St Pierre S., Huidobro-Toro J. P. Endothelin reduces microvascular blood flow by acting on arterioles and venules of the hamster cheek pouch. Eur J Pharmacol. 1990 Nov 6;190(1-2):123–133. doi: 10.1016/0014-2999(90)94119-i. [DOI] [PubMed] [Google Scholar]
  3. Brain S. D., Crossman D. C., Buckley T. L., Williams T. J. Endothelin-1: demonstration of potent effects on the microcirculation of humans and other species. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S147–S150. [PubMed] [Google Scholar]
  4. Brain S. D., Tippins J. R., Williams T. J. Endothelin induces potent microvascular constriction. Br J Pharmacol. 1988 Dec;95(4):1005–1007. doi: 10.1111/j.1476-5381.1988.tb11731.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brain S. D., Williams T. J. Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood flow in rat skin. Br J Pharmacol. 1989 May;97(1):77–82. doi: 10.1111/j.1476-5381.1989.tb11926.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brain S. D., Williams T. J., Tippins J. R., Morris H. R., MacIntyre I. Calcitonin gene-related peptide is a potent vasodilator. Nature. 1985 Jan 3;313(5997):54–56. doi: 10.1038/313054a0. [DOI] [PubMed] [Google Scholar]
  7. Dahlöf B., Gustafsson D., Hedner T., Jern S., Hansson L. Regional haemodynamic effects of endothelin-1 in rat and man: unexpected adverse reaction. J Hypertens. 1990 Sep;8(9):811–817. doi: 10.1097/00004872-199009000-00004. [DOI] [PubMed] [Google Scholar]
  8. Davenport A. P., Maguire J. J. Is endothelin-induced vasoconstriction mediated only by ETA receptors in humans? Trends Pharmacol Sci. 1994 Jan;15(1):9–11. doi: 10.1016/0165-6147(94)90120-1. [DOI] [PubMed] [Google Scholar]
  9. Filep J. G., Sirois M. G., Földes-Filep E., Rousseau A., Plante G. E., Fournier A., Yano M., Sirois P. Enhancement by endothelin-1 of microvascular permeability via the activation of ETA receptors. Br J Pharmacol. 1993 Jul;109(3):880–886. doi: 10.1111/j.1476-5381.1993.tb13657.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fozard J. R., Part M. L. The role of nitric oxide in the regional vasodilator effects of endothelin-1 in the rat. Br J Pharmacol. 1992 Mar;105(3):744–750. doi: 10.1111/j.1476-5381.1992.tb09049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Harrison V. J., Randriantsoa A., Schoeffter P. Heterogeneity of endothelin-sarafotoxin receptors mediating contraction of pig coronary artery. Br J Pharmacol. 1992 Mar;105(3):511–513. doi: 10.1111/j.1476-5381.1992.tb09009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ihara M., Noguchi K., Saeki T., Fukuroda T., Tsuchida S., Kimura S., Fukami T., Ishikawa K., Nishikibe M., Yano M. Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci. 1992;50(4):247–255. doi: 10.1016/0024-3205(92)90331-i. [DOI] [PubMed] [Google Scholar]
  13. Karaki H., Sudjarwo S. A., Hori M., Takai M., Urade Y., Okada T. Induction of endothelium-dependent relaxation in the rat aorta by IRL 1620, a novel and selective agonist at the endothelin ETB receptor. Br J Pharmacol. 1993 Jun;109(2):486–490. doi: 10.1111/j.1476-5381.1993.tb13595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Karne S., Jayawickreme C. K., Lerner M. R. Cloning and characterization of an endothelin-3 specific receptor (ETC receptor) from Xenopus laevis dermal melanophores. J Biol Chem. 1993 Sep 5;268(25):19126–19133. [PubMed] [Google Scholar]
  15. Knock G. A., Terenghi G., Bunker C. B., Bull H. A., Dowd P. M., Polak J. M. Characterization of endothelin-binding sites in human skin and their regulation in primary Raynaud's phenomenon and systemic sclerosis. J Invest Dermatol. 1993 Jul;101(1):73–78. doi: 10.1111/1523-1747.ep12360103. [DOI] [PubMed] [Google Scholar]
  16. Lamping K. G., Clothier J. L., Eastham C. L., Marcus M. L. Coronary microvascular response to endothelin is dependent on vessel diameter and route of administration. Am J Physiol. 1992 Sep;263(3 Pt 2):H703–H709. doi: 10.1152/ajpheart.1992.263.3.H703. [DOI] [PubMed] [Google Scholar]
  17. Lawrence E., Brain S. D. Effect of BQ-123 and Ro 47-0203 (bosentan) on endothelin-induced vasoconstriction in the rat skin. Eur J Pharmacol. 1994 Jul 21;260(1):103–106. doi: 10.1016/0014-2999(94)90017-5. [DOI] [PubMed] [Google Scholar]
  18. Lawrence E., Brain S. D. Responses to endothelins in the rat cutaneous microvasculature: a modulatory role of locally-produced nitric oxide. Br J Pharmacol. 1992 Jul;106(3):733–738. doi: 10.1111/j.1476-5381.1992.tb14402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller R. C., Pelton J. T., Huggins J. P. Endothelins--from receptors to medicine. Trends Pharmacol Sci. 1993 Feb;14(2):54–60. doi: 10.1016/0165-6147(93)90031-e. [DOI] [PubMed] [Google Scholar]
  20. Moreland S., McMullen D. M., Delaney C. L., Lee V. G., Hunt J. T. Venous smooth muscle contains vasoconstrictor ETB-like receptors. Biochem Biophys Res Commun. 1992 Apr 15;184(1):100–106. doi: 10.1016/0006-291x(92)91163-k. [DOI] [PubMed] [Google Scholar]
  21. Randall M. D., Douglas S. A., Hiley C. R. Vascular activities of endothelin-1 and some alanyl substituted analogues in resistance beds of the rat. Br J Pharmacol. 1989 Oct;98(2):685–699. doi: 10.1111/j.1476-5381.1989.tb12644.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Riezebos J., Watts I. S., Vallance P. J. Endothelin receptors mediating functional responses in human small arteries and veins. Br J Pharmacol. 1994 Feb;111(2):609–615. doi: 10.1111/j.1476-5381.1994.tb14780.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sakurai T., Yanagisawa M., Takuwa Y., Miyazaki H., Kimura S., Goto K., Masaki T. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990 Dec 20;348(6303):732–735. doi: 10.1038/348732a0. [DOI] [PubMed] [Google Scholar]
  24. 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,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor. Biochem Biophys Res Commun. 1992 Apr 30;184(2):953–959. doi: 10.1016/0006-291x(92)90683-c. [DOI] [PubMed] [Google Scholar]
  25. Takayanagi R., Kitazumi K., Takasaki C., Ohnaka K., Aimoto S., Tasaka K., Ohashi M., Nawata H. Presence of non-selective type of endothelin receptor on vascular endothelium and its linkage to vasodilation. FEBS Lett. 1991 Apr 22;282(1):103–106. doi: 10.1016/0014-5793(91)80454-b. [DOI] [PubMed] [Google Scholar]
  26. Wenzel R. R., Noll G., Lüscher T. F. Endothelin receptor antagonists inhibit endothelin in human skin microcirculation. Hypertension. 1994 May;23(5):581–586. doi: 10.1161/01.hyp.23.5.581. [DOI] [PubMed] [Google Scholar]
  27. Williams D. L., Jr, Jones K. L., Pettibone D. J., Lis E. V., Clineschmidt B. V. Sarafotoxin S6c: an agonist which distinguishes between endothelin receptor subtypes. Biochem Biophys Res Commun. 1991 Mar 15;175(2):556–561. doi: 10.1016/0006-291x(91)91601-8. [DOI] [PubMed] [Google Scholar]
  28. Williams T. J. Proceedings:Simultaneous measurement of local plasma exudation and blood flow changes induced by intradermal injection of vasoactive substances, using [131I]albumen and 133Xe. J Physiol. 1976 Jan;254(1):4P–5P. [PubMed] [Google Scholar]

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