Response-selective C5a agonists: Differential effects on neutropenia and hypotension in the rat

Anna J. Short, Natalii J. Paczkowski, Shawn M. Vogen, Sam D. Sanderson, Stephen M. Taylor

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Some in vivo activities of two complement C5a agonist analogues have been evaluated by measuring changes in blood pressure and neutropenia in the rat and comparing the results with their receptor affinities in peritoneal macrophages and polymorphonuclear leucocytes (PMNs). In vitro C5a receptor (C5aR) binding experiments showed that YSFKPMPLaR and YSFKD(NMeNle)PlaR had similar affinities for the macrophage C5aR (IC50 0.2, 0.1 μM respectively). In PMNs, the affinity of YSFKPMPLaR (IC50 0.1 μM) was similar to that in macrophages, whereas the affinity of YSFKD(NMeNle)PLaR for the PMN C5aR was > 100 μM. Given i.v., YSFKD(NMeNle)PLaR had similar activity to YSFKPMPLaR on blood pressure but did not cause neutropenia. These results demonstrate selectivity of a new C5a agonist in vitro, which is paralleled in vivo. The results suggest the possibility of developing selective agonists of C5a for in vivo use in humans.

Original languageEnglish (US)
Pages (from-to)511-514
Number of pages4
JournalBritish Journal of Pharmacology
Volume128
Issue number3
DOIs
StatePublished - Nov 9 1999
Externally publishedYes

Keywords

  • C5a
  • C5a agonist
  • Hypotension
  • Neutropenia

ASJC Scopus subject areas

  • Pharmacology

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    Short, A. J., Paczkowski, N. J., Vogen, S. M., Sanderson, S. D., & Taylor, S. M. (1999). Response-selective C5a agonists: Differential effects on neutropenia and hypotension in the rat. British Journal of Pharmacology, 128(3), 511-514. https://doi.org/10.1038/sj.bjp.0702847