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. 1994 Jun;112(2):704–708. doi: 10.1111/j.1476-5381.1994.tb13133.x

Evidence for a differential location of vasoconstrictor endothelin receptors in the vasculature.

S Moreland 1, D McMullen 1, B Abboa-Offei 1, A Seymour 1
PMCID: PMC1910356  PMID: 8075891

Abstract

1. There are at least two subtypes of vascular endothelin (ET) receptors. Stimulation of the ETA receptors on vascular smooth muscle cells leads to vasoconstriction, whereas activation of the ETB receptors on endothelial cells elicits vasodilatation. Several reports in the literature have suggested the presence of a vasoconstrictor non-ETA receptor on vascular smooth muscle which has pharmacological similarities to the ETB receptor. The present study was undertaken to determine the location of this ETB-like receptor within the vascular system. 2. Fourteen vascular smooth muscle preparations from six species were used to determine the effect of the ETA receptor antagonist, BQ-123, on concentration-response curves elicited by ET-1 and the ability of the ETB receptor agonist, sarafotoxin S6c, to cause contraction. The vessels fell into two categories. One group was sensitive to BQ-123 and insensitive to sarafotoxin S6c and, thus, probably contained ETA receptors. The other group, with vasoconstrictor ETB-like receptors, was insensitive to BQ-123 and sensitive to sarafotoxin S6c. 3. Vessels from cynomolgus monkeys, when studied in vitro, appeared to contain primarily ETA receptors, although the potency of BQ-123 was quite variable, suggesting the possibility of ETA receptor subtypes. In contrast, both ET-1 and sarafotoxin S6c, given as intravenous injections in conscious monkeys, produced transient, equipotent, and dose-related increases in blood pressure. The highest dose of sarafotoxin S6c (1 nmol kg-1, i.v.) also caused a marked secondary depressor response (-80 +/- 6 mmHg) that lasted approximately 10 min. The pressor responses suggest that the vasoconstrictor ETB-like receptors are present in cynomolgus monkeys.(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. Clozel M., Gray G. A., Breu V., Löffler B. M., Osterwalder R. The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun. 1992 Jul 31;186(2):867–873. doi: 10.1016/0006-291x(92)90826-7. [DOI] [PubMed] [Google Scholar]
  3. Donckier J. E., Hanet C., Berbinschi A., Galanti L., Robert A., Van Mechelen H., Pouleur H., Ketelslegers J. M. Cardiovascular and endocrine effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations in conscious dogs. Circulation. 1991 Dec;84(6):2476–2484. doi: 10.1161/01.cir.84.6.2476. [DOI] [PubMed] [Google Scholar]
  4. Eglezos A., Cucchi P., Patacchini R., Quartara L., Maggi C. A., Mizrahi J. Differential effects of BQ-123 against endothelin-1 and endothelin-3 on the rat vas deferens: evidence for an atypical endothelin receptor. Br J Pharmacol. 1993 Jul;109(3):736–738. doi: 10.1111/j.1476-5381.1993.tb13635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goetz K. L., Wang B. C., Madwed J. B., Zhu J. L., Leadley R. J., Jr Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol. 1988 Dec;255(6 Pt 2):R1064–R1068. doi: 10.1152/ajpregu.1988.255.6.R1064. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Hay D. W. Pharmacological evidence for distinct endothelin receptors in guinea-pig bronchus and aorta. Br J Pharmacol. 1992 Aug;106(4):759–761. doi: 10.1111/j.1476-5381.1992.tb14407.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. King A. J., Brenner B. M., Anderson S. Endothelin: a potent renal and systemic vasoconstrictor peptide. Am J Physiol. 1989 Jun;256(6 Pt 2):F1051–F1058. doi: 10.1152/ajprenal.1989.256.6.F1051. [DOI] [PubMed] [Google Scholar]
  11. Lin H. Y., Kaji E. H., Winkel G. K., Ives H. E., Lodish H. F. Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3185–3189. doi: 10.1073/pnas.88.8.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moreland R. S., Cilea J., Moreland S. Staurosporine decreases stiffness but not stress in endothelin-1-stimulated arterial muscle. Am J Physiol. 1992 Apr;262(4 Pt 1):C862–C869. doi: 10.1152/ajpcell.1992.262.4.C862. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Panek R. L., Major T. C., Hingorani G. P., Doherty A. M., Taylor D. G., Rapundalo S. T. Endothelin and structurally related analogs distinguish between endothelin receptor subtypes. Biochem Biophys Res Commun. 1992 Mar 16;183(2):566–571. doi: 10.1016/0006-291x(92)90519-q. [DOI] [PubMed] [Google Scholar]
  15. Saeki T., Ihara M., Fukuroda T., Yamagiwa M., Yano M. [Ala1,3,11,15]endothelin-1 analogs with ETB agonistic activity. Biochem Biophys Res Commun. 1991 Aug 30;179(1):286–292. doi: 10.1016/0006-291x(91)91367-l. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Scalese R. J., DeForrest J. M., Hammerstone S., Parente E., Burkett D. E. Long term vascular catheterization of the cynomolgus monkey. Lab Anim Sci. 1990 Sep;40(5):530–532. [PubMed] [Google Scholar]
  18. Sogabe K., Nirei H., Shoubo M., Nomoto A., Ao S., Notsu Y., Ono T. Pharmacological profile of FR139317, a novel, potent endothelin ETA receptor antagonist. J Pharmacol Exp Ther. 1993 Mar;264(3):1040–1046. [PubMed] [Google Scholar]
  19. Sumner M. J., Cannon T. R., Mundin J. W., White D. G., Watts I. S. Endothelin ETA and ETB receptors mediate vascular smooth muscle contraction. Br J Pharmacol. 1992 Nov;107(3):858–860. doi: 10.1111/j.1476-5381.1992.tb14537.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]

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