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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1990 May;100(1):163–167. doi: 10.1111/j.1476-5381.1990.tb12070.x

Influence of plasma protein content and platelet number on the potency of PAF and its antagonist RP 59227 in rabbit platelet preparations.

A Floch 1, I Cavero 1
PMCID: PMC1917445  PMID: 2372657

Abstract

1. The potency of platelet activating factor (PAF) as a pro-aggregatory agent and of RP 59227, a selective antagonist of PAF-induced platelet aggregation, was determined in several types of rabbit platelet preparations. 2. PAF produced concentration-dependent responses irrespective of whether the suspension medium for the platelets (200,000 per microliter) was undiluted plasma (PRP), saline-diluted plasma (dil. PRP) or a salt solution (WP: washed platelets). The potency of PAF, expressed as pD2, was 3 fold higher in WP than PRP or diluted PRP (dil. PRP) for which the ratio (v/v) of total plasma to saline was 1:1.5. In PRP and WP preparations, an increase in the number of platelets in the reaction medium from 200,000 to 600,000 enhanced the potency of PAF slightly (2.3 fold). Furthermore, PAF was 3 times more potent in WP than PRP when studied in preparations containing either 200,000, 400,000 or 600,000 platelets per microliter. 3. RP 59227, like the reference compounds WEB 2086 and CV-6209, behaved as a competitive antagonist against PAF-evoked platelet aggregation in PRP, WP and dil. PRP (200,000 platelets per microliter). Their potency was slightly greater (1.6 to 2.6 fold more) in dil. PRP than in WP, but in PRP it was 3.5 to 4.3 times lower than in WP. RP 59227 was 2.3 and 5.0 times less potent when the platelet number of the PRP suspension was increased from 200,000 to 400,000 and 600,000 per microliter, respectively, whereas the potency of RP 59227 in WP was not modified by these changes in platelet number.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ardlie N. G., Packham M. A., Mustard J. F. Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. Br J Haematol. 1970 Jul;19(1):7–17. doi: 10.1111/j.1365-2141.1970.tb01596.x. [DOI] [PubMed] [Google Scholar]
  3. Casals-Stenzel J., Muacevic G., Weber K. H. Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor. J Pharmacol Exp Ther. 1987 Jun;241(3):974–981. [PubMed] [Google Scholar]
  4. Cheng Y., Prusoff W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973 Dec 1;22(23):3099–3108. doi: 10.1016/0006-2952(73)90196-2. [DOI] [PubMed] [Google Scholar]
  5. Homma H., Tokumura A., Hanahan D. J. Binding and internalization of platelet-activating factor 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine in washed rabbit platelets. J Biol Chem. 1987 Aug 5;262(22):10582–10587. [PubMed] [Google Scholar]
  6. Kenakin T. P. The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev. 1984 Sep;36(3):165–222. [PubMed] [Google Scholar]
  7. Lambrecht G., Parnham M. J. Kadsurenone distinguishes between different platelet activating factor receptor subtypes on macrophages and polymorphonuclear leucocytes. Br J Pharmacol. 1986 Feb;87(2):287–289. doi: 10.1111/j.1476-5381.1986.tb10816.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Marquis O., Robaut C., Cavero I. Evidence for the existence and ionic modulation of platelet-activating factor receptors mediating degranulatory responses in human polymorphonuclear leukocytes. J Pharmacol Exp Ther. 1989 Jul;250(1):293–300. [PubMed] [Google Scholar]
  9. O'Donnell S. R., Barnett C. J. pA2 values for antagonists of platelet activating factor on aggregation of rabbit platelets. Br J Pharmacol. 1988 Jun;94(2):437–442. doi: 10.1111/j.1476-5381.1988.tb11545.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Robaut C., Durand G., James C., Lave D., Sedivy P., Floch A., Mondot S., Pacot D., Cavero I., Le Fur G. PAF binding sites. Characterization by [3H]52770 RP, a pyrrolo[1,2-c]thiazole derivative, in rabbit platelets. Biochem Pharmacol. 1987 Oct 1;36(19):3221–3229. doi: 10.1016/0006-2952(87)90637-x. [DOI] [PubMed] [Google Scholar]
  11. Stewart A. G., Dusting G. J. Characterization of receptors for platelet-activating factor on platelets, polymorphonuclear leukocytes and macrophages. Br J Pharmacol. 1988 Aug;94(4):1225–1233. doi: 10.1111/j.1476-5381.1988.tb11642.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Tahraoui L., Floch A., Mondot S., Cavero I. High affinity specific binding sites for tritiated platelet-activating factor in canine platelet membranes: counterparts of platelet-activating factor receptors mediating platelet aggregation. Mol Pharmacol. 1988 Aug;34(2):145–151. [PubMed] [Google Scholar]
  13. Terashita Z., Imura Y., Takatani M., Tsushima S., Nishikawa K. CV-6209, a highly potent antagonist of platelet activating factor in vitro and in vivo. J Pharmacol Exp Ther. 1987 Jul;242(1):263–268. [PubMed] [Google Scholar]
  14. Tokumura A., Yoshida J., Maruyama T., Fukuzawa K., Tsukatani H. Platelet aggregation induced by ether-linked phospholipids. 1. Inhibitory actions of bovine serum albumin and structural analogues of platelet activating factor. Thromb Res. 1987 Apr 1;46(1):51–63. doi: 10.1016/0049-3848(87)90206-4. [DOI] [PubMed] [Google Scholar]

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