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. 1993 Oct;110(2):783–789. doi: 10.1111/j.1476-5381.1993.tb13880.x

Characterization of endothelin receptors mediating the effects of the endothelin/sarafotoxin peptides on autonomic neurotransmission in the rat vas deferens and guinea-pig ileum.

T D Warner 1, G H Allcock 1, E J Mickley 1, J R Vane 1
PMCID: PMC2175961  PMID: 8242252

Abstract

1. To characterize the receptors mediating the effects of the endothelin/sarafotoxin family of peptides on the responses to electrical stimulation of the rat vas deferens (RVD) and guinea-pig ileum (GPI) we have used endothelin-1 (ET-1), ET-3, sarafotoxin 6b (SX6b) and SX6c as agonists and the endothelin-receptor antagonists BQ-123 (ETA receptor selective) and PD 142893 (non-selective). 2. In the RVD, ET-1 and SX6b increased the twitches induced by field stimulation starting at a threshold concentration of 10(-10) M while the threshold concentration for ET-3 was 3 x 10(-9) M. SX6c (up to 3 x 10(-8) M) did not potentiate the twitches. SX6b produced significantly (P < 0.05) greater potentiations than ET-1 at concentrations of 3 x 10(-9) M and higher, and 10(-7) M ET-3 also produced a significantly greater effect than ET-1 at the same concentration. Thus, at threshold the rank order of peptides was ET-1 = SX6b > ET-3 >>> SX6c, and at concentrations of 3 x 10(-8) M and higher, SX6b > ET-3 > ET-1 >>> SX6c. 3. In the presence of BQ-123 or PD 142893 (10(-5) M) the threshold concentrations for ET-1 to augment the twitches were increased 30 fold. In the same conditions neither SX6b nor ET-3 potentiated the responses. The relative activities of the endothelin/sarafotoxin peptides and the effectiveness of the endothelin receptor antagonists are consistent with postjunctional ETA receptors mediating these effects.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Ambar I., Kloog Y., Schvartz I., Hazum E., Sokolovsky M. Competitive interaction between endothelin and sarafotoxin: Binding and phosphoinositides hydrolysis in rat atria and brain. Biochem Biophys Res Commun. 1989 Jan 16;158(1):195–201. doi: 10.1016/s0006-291x(89)80197-4. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Cody W. L., Doherty A. M., He J. X., DePue P. L., Rapundalo S. T., Hingorani G. A., Major T. C., Panek R. L., Dudley D. T., Haleen S. J. Design of a functional hexapeptide antagonist of endothelin. J Med Chem. 1992 Aug 21;35(17):3301–3303. doi: 10.1021/jm00095a029. [DOI] [PubMed] [Google Scholar]
  5. Guimarães C. L., Rae G. A. Dual effects of endothelins -1, -2 and -3 on guinea pig field-stimulated ileum: possible mediation by two receptors coupled to pertussis toxin-insensitive mechanisms. J Pharmacol Exp Ther. 1992 Jun;261(3):1253–1259. [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Maggi C. A., Giuliani S., Patacchini R., Rovero P., Giachetti A., Meli A. The activity of peptides of the endothelin family in various mammalian smooth muscle preparations. Eur J Pharmacol. 1989 Dec 12;174(1):23–31. doi: 10.1016/0014-2999(89)90869-8. [DOI] [PubMed] [Google Scholar]
  9. Matsumoto H., Suzuki N., Onda H., Fujino M. Abundance of endothelin-3 in rat intestine, pituitary gland and brain. Biochem Biophys Res Commun. 1989 Oct 16;164(1):74–80. doi: 10.1016/0006-291x(89)91684-7. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Rae G. A., Calixto J. B. Effects of endothelins on nerve-mediated contractions of the mouse vas deferens. Life Sci. 1990;47(17):PL83–PL89. doi: 10.1016/0024-3205(90)90191-s. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. Tabuchi Y., Nakamaru M., Rakugi H., Nagano M., Mikami H., Ogihara T. Endothelin inhibits presynaptic adrenergic neurotransmission in rat mesenteric artery. Biochem Biophys Res Commun. 1989 Jun 15;161(2):803–808. doi: 10.1016/0006-291x(89)92671-5. [DOI] [PubMed] [Google Scholar]
  16. Télémaque S., D'Orléans-Juste P. Presence of a phosphoramidon-sensitive endothelin-converting enzyme which converts big-endothelin-1, but not big-endothelin-3, in the rat vas deferens. Naunyn Schmiedebergs Arch Pharmacol. 1991 Oct;344(4):505–507. doi: 10.1007/BF00172593. [DOI] [PubMed] [Google Scholar]
  17. Wiklund N. P., Ohlén A., Cederqvist B. Inhibition of adrenergic neuroeffector transmission by endothelin in the guinea-pig femoral artery. Acta Physiol Scand. 1988 Oct;134(2):311–312. doi: 10.1111/j.1748-1716.1988.tb08495.x. [DOI] [PubMed] [Google Scholar]
  18. Wiklund N. P., Ohlén A., Wiklund C. U., Hedqvist P., Gustafsson L. E. Endothelin modulation of neuroeffector transmission in rat and guinea pig vas deferens. Eur J Pharmacol. 1990 Aug 21;185(1):25–33. doi: 10.1016/0014-2999(90)90207-m. [DOI] [PubMed] [Google Scholar]
  19. Wiklund N. P., Wiklund C. U., Cederqvist B., Ohlén A., Hedqvist P., Gustafsson L. E. Endothelin modulation of neuroeffector transmission in smooth muscle. J Cardiovasc Pharmacol. 1991;17 (Suppl 7):S335–S339. doi: 10.1097/00005344-199100177-00096. [DOI] [PubMed] [Google Scholar]
  20. Wiklund N. P., Wiklund C. U., Ohlén A., Gustafsson L. E. Cholinergic neuromodulation by endothelin in guinea pig ileum. Neurosci Lett. 1989 Jul 3;101(3):342–346. doi: 10.1016/0304-3940(89)90557-0. [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]
  22. Wollberg Z., Bdolah A., Galron R., Sokolovsky M., Kochva E. Contractile effects and binding properties of endothelins/sarafotoxins in the guinea pig ileum. Eur J Pharmacol. 1991 May 30;198(1):31–36. doi: 10.1016/0014-2999(91)90558-8. [DOI] [PubMed] [Google Scholar]

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