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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Short, A. Haaima, G. Finch, A. M. Shiels, I. A. Taylor, S. M. Wong, A. K. Fairlie, D. P. |
| Description | Author Affiliation: Short A ( Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Australia.) |
| Abstract | A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D-cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to antagonize the neutropenic effects of both C5a and endotoxin in rats. Human recombinant C5a (2 microg kg(-1) i.v.) caused rapid neutropenia, characterized by an 83% decrease in circulating polymorphonuclear leukocytes (PMNs) at 5 min. Administration of F-[OPdChaWR] (0.3-3 mg kg(-1) i.v.), did not affect the levels of circulating PMNs but, when given 10 min prior to C5a, it inhibited the C5a-induced neutropenia by up to 70%. Administration of E. Coli lipopolysaccharide (LPS, 1 mg kg(-1) i.v.) also caused neutropenia with an 88% decrease in circulating PMNs after 30 min. When rats were pretreated with F-[OPdChaWR] (0.3 - 10 mg kg(-1) i.v.) 10 min prior to LPS, there was a dose-dependent antagonism of the neutropenia caused by LPS, with up to 69% reversal of neutropenia observed 30 min after LPS administration. These findings suggest that C5a receptor antagonists may have therapeutic potential in the many diseases known to involve either endotoxin or C5a. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD Chemistry Complement C5a Adverse Effects Endotoxins Neutropenia Prevention & Control Receptors, Complement Serine Endopeptidases Pharmacology Animals Antagonists & Inhibitors Complement Inactivator Proteins Dose-Response Relationship, Drug Leukocyte Count Drug Effects Lipopolysaccharides N-Formylmethionine Leucyl-Phenylalanine Metabolism Chemically Induced Neutrophils Cytology Rats, Wistar Receptor, Anaphylatoxin C5a Recombinant Proteins Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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