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Clonidine increases membrane-associated phospholipase A2

Published online by Cambridge University Press:  25 November 2005

U. S. R. Helfrich ,
M. Schley ,
G. A. Petroianu ,
J. Schmeck  and
C. Konrad
U. S. R. Helfrich
Affiliation:
University of Heidelberg, Faculty of Clinical Medicine Mannheim, Department of Anaesthesiology and Operative Intensive Care Medicine, Mannheim, Germany
M. Schley
Affiliation:
University of Heidelberg, Faculty of Clinical Medicine Mannheim, Department of Anaesthesiology and Operative Intensive Care Medicine, Mannheim, Germany
G. A. Petroianu
Affiliation:
United Arab Emirates University, Department of Pharmacology, Al Ain, UAE
J. Schmeck
Affiliation:
University of Mainz, Department of Anaesthesiology, Faculty of Clinical Medicine Mannheim, Mainz, Germany
C. Konrad
Affiliation:
University of Heidelberg, Faculty of Clinical Medicine Mannheim, Department of Anaesthesiology and Operative Intensive Care Medicine, Mannheim, Germany
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Extract

Summary

Background and objective: An anti-inflammatory effect of α2-adrenoreceptor agonists has been suggested. Phospholipase A2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A2 activity in an established in vitro model. Methods: Human being platelet membranes containing active phospholipase A2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A2 was measured by a radioisotope technique. Results: A massive increase in phospholipase A2 activity was measured after clonidine exposure leading to final values of 92.5 ± 3.1 pmol mg protein−1 min−1 (4.5-fold higher than control values; P ≤ 0.01 vs. control). After clonidine exposure the maximal reaction velocity increased, while the Michaelis–Menten constant did not change. The Lineweaver–Burk representation suggested an interaction of clonidine with the phospholipase A2–substrate complex as well as the phospholipase A2 molecule. Conclusion: We conclude that the putative anti-inflammatory effect of clonidine was not caused by inhibition of phospholipase A2.

Keywords

PHOSPHOLIPASES A, phospholipase A2CLONIDINEINFLAMMATIONPLATELETS
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 12 , December 2005 , pp. 942 - 946
Copyright
© 2005 European Society of Anaesthesiology

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References

Materson BJ, Reda DJ, Cushman WC. Single-drug therapy for hypertension in men. N Engl J Med 1993; 328: 914–921.Google Scholar
Webster J, Koch HF. Aspects of tolerability of centrally acting antihypertensive drugs. J Cardiovasc Pharm 1996; 27: 49–54.Google Scholar
Reis DJ, Regunathan S, Meeley MP. Imidazole receptors and clonidine-displacing substance in relationship to control of blood pressure, neuroprotection, and adrenomedullary secretion. Am J Hypertens 1992; 5: 51S–57S.Google Scholar
Culebras X, Van Gessel E, Hoffmeyer P, Gamulin Z. Clonidine combined with long acting anesthetic does not prolong postoperative analgesia after brachial plexus blocks but does induce hemodynamic changes. Anesth Analg 2001; 92: 199–204.Google Scholar
El Saied AH, Steyn MP, Ansermino JM. Clonidine prolongs the effect of ropivacaine for axillary brachial plexus blockade. Can J Anaesth 2000; 47: 962–967.Google Scholar
Akhondzadeh S, Ahmadi-Abhari SA, Assadi SM, Shabestari OL, Kashani AR, Farzanehgan ZM. Double-blind randomized controlled trial of baclofen versus clonidine in the treatment of opiates withdrawal. J Clin Pharm Ther 2000; 25: 347–353.Google Scholar
Berggren U, Fahlke C, Norrby A, Zachrisson O, Balldin J. Subsensitive alpha-2-adrenoceptor function in male alcohol-dependent individuals during 6 months of abstinence. Drug Alcohol Depend 2000; 57: 255–260.Google Scholar
Falhke C, Berggren U, Balldin J. Cardiovascular responces to clonidine in alcohol withdrawal: are they related to psychopathology and mental well-being? Alcohol 2000; 21: 231–237.Google Scholar
Holsapple MP, Malave A, Lowry MT, Kim GKW. Central and peripheral antiinflammatory actions by clonidine and structurally related imidazoline analog. J Pharmacol Exp Ther 1984; 229: 399–403.Google Scholar
Holsapple MP, Trizzino J, Nichols DE, Kim GKW. Therapeutic and adjuvantive applications of an imidazoline antiinflammatory agent. J Pharmacol Exp Ther 1983; 224: 567–571.Google Scholar
Kulkarni SK, Mehta AK, Kunchandry J. Antiinflammatory actions of clonidine, guanfacine and B-HT 920 against various inflammagen-induced acute paw edema in rats. Arch Int Pharmacodyn Ther 1986; 279: 324–334.Google Scholar
Heller A, Koch T, Schmeck J, van Ackern K. Lipid mediators in inflammatory disorders. Drugs 1998; 55: 487–496.Google Scholar
Chang J, Blazek E, Skowronek M, Marinari L, Carlson RP. The antiinflammatory action of guanabenz is mediated through 5-lipogenase and cyclooxygenase inhibition. Eur J Pharmacol 1987; 142: 197–205.Google Scholar
Robert B, Petit JY, Grimanud N, Juge M, Welin L. Effects of clonidine on experimental brain edema in the rat. Agents Actions 1992; 37: 268–272.Google Scholar
Petroianu G, Helfrich U, Schmitt A, Bergler W, Rufer R. Dose-dependent inhibition of phospholipase A2 by paraoxon in vitro: prelimary results. J Appl Toxicol 1997; 17: 421–424.Google Scholar
Flesch I, Schmidt B, Ferber E. Acyl chain specificity and kinetic properties of phospholipase A1 and A2 of bone marrow derived macrophages. Z Naturforsch 1985; 40c: 356–363.Google Scholar
Sundaram GS, Shakir KMM, Barnes G, Margolis S. Release of phospholipase A2, and triglyceride lipase from rat liver. Biol Chem 1978; 253: 7703–7710.Google Scholar
MacPherson RD. The pharmacological basis of contemporary pain mangement. Pharmacol Ther 2000; 88: 163–185.Google Scholar
Dahl V, Raeder JC. Non-opioid postoperative analgesia. Acta Anaesthesiol Scand 2000; 44: 1191–1203.Google Scholar
Tejwani GA, Rattan AK. Antagonism of antinociception produced by intrathecal clonidine by ketorolac in the rat: the role of the opioid system. Anesth Analg 2000; 90: 1152–1156.Google Scholar
Mendez R, Eisenach JC, Kashtan K. Epidural clonidine analgesia after caesarean section. Anesthesiology 1990; 73: 848–852.Google Scholar
Filos KS, Goudas LC, Patroni O, Polyzou V. Hemodynamic and analgesic profile after intrathecal clonidine in humans. A dose-response study. Anesthesiology 1994; 81: 591–601.Google Scholar
Piper SN, Suttner SW, Schmidt CC, Maleck WH, Kumle B, Boldt J. Nefopam and clonidine in the prevention of postanaesthetic shivering. Anaesthesia 1999; 54: 683–702.Google Scholar
Piper SN, Röhm KD, Suttner SW, Maleck WH, Kranke P, Boldt J. A comparison of nefopam and clonidine for the prevention of postanaesthetic shivering: a comparative, double-blind and placebo-controlled dose-ranging study. Anaesthesia 2004; 59: 559–564.Google Scholar
Lowenthal DT, Matzek KM, MacGregor TR. Clinical pharmakokinetics of clonidine. Clin Pharmacokinet 1988; 14: 287–310.Google Scholar
Zielmann S, Petrow H, Walther P, Henze T. Intensive care delirium syndromes. Anaesthesiol Reanim 2003; 28: 8–12.Google Scholar
Pruzanski W, Vadas P, Stefanski E, Urowitz MB. Phospholipase A2 activity in sera and synovial fluids in rheumatoid arthritis and osteoarthritis. Its possible role as a proinflammatory enzyme. Rheumatol 1985; 12: 211–216.Google Scholar
Pruzanski W, Vadas P, Browning J. Secretory non-pancreatic group II phospholipase A2: role in physiologic and inflammatory processes. J Lipid Mediat 1993; 8: 161–167.Google Scholar
Vadas P, Pruzanski W, Farewell V. A predictive model for the clearance of soluble phospholipase A2 during septic shock. J Clin Lab Med 1991; 118: 471–475.Google Scholar
Taube C, Hauser A, Dunemann A, Forster W. Changes in prostaglandin synthesis in aorta, brain, kidney medulla of normal rats treated with antihypertensive drugs. Acta Biol Med Ger 1978; 37: 889–890.Google Scholar