Skip to main content
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1993;2(2):103–107. doi: 10.1155/S0962935193000146

Inhibition of smooth muscle contraction and platelet aggregation by peptide 204–212 of lipocortin 5: an attempt to define some structure requirements

K G Mugridge 3, C Becherucci 2, L Parente 2, M Perretti 1,
PMCID: PMC2365395  PMID: 18475510

Abstract

Peptide 204–212 of lipocortin (LC) 5 inhibited porcine pancreatic phospholipase A2 (PLA2) induced rat stomach strip contractions and ADP induced rabbit platelet aggregation in a concentration dependent manner (IC30 of 10 μM and 400 μM, respectively). The first two amino acids are not necessary since the eptapeptide 206–212 was equipotent in both assays (IC30 of 12.5 μM and 420 μM). Of the two pentapeptides 204–208 and 208–212 only the latter showed inhibitory activity in both models although the potency was much reduced (IC30 of 170 μM and 630 μM) compared with that of the parent nonapeptide. Comparison of peptide 204–212 effects with those of its analogues on LC1 and LC2 indicate that lysine 208 and aspartic acid 211 are essential in order to maintain a fully active nonapeptide.

Full Text

The Full Text of this article is available as a PDF (424.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barton G. J., Newman R. H., Freemont P. S., Crumpton M. J. Amino acid sequence analysis of the annexin super-gene family of proteins. Eur J Biochem. 1991 Jun 15;198(3):749–760. doi: 10.1111/j.1432-1033.1991.tb16076.x. [DOI] [PubMed] [Google Scholar]
  2. Cabré F., Moreno J. J., Carabaza A., Ortega E., Mauleón D., Carganico G. Antiflammins. Anti-inflammatory activity and effect on human phospholipase A2. Biochem Pharmacol. 1992 Aug 4;44(3):519–525. doi: 10.1016/0006-2952(92)90444-n. [DOI] [PubMed] [Google Scholar]
  3. Chan C. C., Ni M., Miele L., Cordella-Miele E., Ferrick M., Mukherjee A. B., Nussenblatt R. B. Effects of antiflammins on endotoxin-induced uveitis in rats. Arch Ophthalmol. 1991 Feb;109(2):278–281. doi: 10.1001/archopht.1991.01080020124058. [DOI] [PubMed] [Google Scholar]
  4. Cirino G., Peers S. H., Flower R. J., Browning J. L., Pepinsky R. B. Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test. Proc Natl Acad Sci U S A. 1989 May;86(9):3428–3432. doi: 10.1073/pnas.86.9.3428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Douglas G. J., Flower R. J., Parente L., Perretti M. Peptide 204-212 of lipocortin 5 inhibits the generation of a prostacyclin-like factor from rat aorta preparations in vitro. Prostaglandins. 1992 Nov;44(5):381–388. doi: 10.1016/0090-6980(92)90134-f. [DOI] [PubMed] [Google Scholar]
  6. Errasfa M., Russo-Marie F. A purified lipocortin shares the anti-inflammatory effect of glucocorticosteroids in vivo in mice. Br J Pharmacol. 1989 Aug;97(4):1051–1058. doi: 10.1111/j.1476-5381.1989.tb12561.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Funakoshi T., Abe M., Sakata M., Shoji S., Kubota Y., Shimada H., Kojima S. Novel anticoagulant peptides from the functional site of human placental anticoagulant protein. Biochem Int. 1991 May;24(1):173–180. [PubMed] [Google Scholar]
  8. Funakoshi T., Abe M., Sakata M., Shoji S., Kubota Y. The functional site of placental anticoagulant protein: essential histidine residue of placental anticoagulant protein. Biochem Biophys Res Commun. 1990 Apr 16;168(1):125–134. doi: 10.1016/0006-291x(90)91683-j. [DOI] [PubMed] [Google Scholar]
  9. Lloret S., Moreno J. J. In vitro and in vivo effects of the anti-inflammatory peptides, antiflammins. Biochem Pharmacol. 1992 Oct 6;44(7):1437–1441. doi: 10.1016/0006-2952(92)90546-u. [DOI] [PubMed] [Google Scholar]
  10. Miele L., Cordella-Miele E., Facchiano A., Mukherjee A. B. Novel anti-inflammatory peptides from the region of highest similarity between uteroglobin and lipocortin I. Nature. 1988 Oct 20;335(6192):726–730. doi: 10.1038/335726a0. [DOI] [PubMed] [Google Scholar]
  11. Parente L., Becherucci C., Perretti M., Solito E., Mugridge K. G., Galeotti C. L., Raugei G., Melli M., Sanso M. Are the lipocortins the second messengers of the anti-inflammatory action of glucocorticoids? Prog Clin Biol Res. 1990;349:55–68. [PubMed] [Google Scholar]
  12. Pepinsky R. B., Tizard R., Mattaliano R. J., Sinclair L. K., Miller G. T., Browning J. L., Chow E. P., Burne C., Huang K. S., Pratt D. Five distinct calcium and phospholipid binding proteins share homology with lipocortin I. J Biol Chem. 1988 Aug 5;263(22):10799–10811. [PubMed] [Google Scholar]
  13. Perretti M., Becherucci C., Mugridge K. G., Solito E., Silvestri S., Parente L. A novel anti-inflammatory peptide from human lipocortin 5. Br J Pharmacol. 1991 Jun;103(2):1327–1332. doi: 10.1111/j.1476-5381.1991.tb09788.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Tetta C., Camussi G., Bussolino F., Herrick-Davis K., Baglioni C. Inhibition of the synthesis of platelet-activating factor by anti-inflammatory peptides (antiflammins) without methionine. J Pharmacol Exp Ther. 1991 May;257(2):616–620. [PubMed] [Google Scholar]
  15. Vargas J. R., Radomski M., Moncada S. The use of prostacyclin in the separation from plasma and washing of human platelets. Prostaglandins. 1982 Jun;23(6):929–945. doi: 10.1016/0090-6980(82)90135-6. [DOI] [PubMed] [Google Scholar]
  16. Vostal J. G., Mukherjee A. B., Miele L., Shulman N. R. Novel peptides derived from a region of local homology between uteroglobin and lipocortin-1 inhibit platelet aggregation and secretion. Biochem Biophys Res Commun. 1989 Nov 30;165(1):27–36. doi: 10.1016/0006-291x(89)91029-2. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES