Clonidine increases membrane-associated phospholipase A 2.
OBJECTIVE
An anti-inflammatory effect of alpha2-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 < or = 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.


CONCLUSIONS
We conclude that the putative anti-inflammatory effect of clonidine was not caused by inhibition of phospholipase A2.
Helfrich
U S R
US
University of Heidelberg, Faculty of Clinical Medicine Mannheim, Department of Anaesthesiology and Operative Intensive Care Medicine, Mannheim, Germany.
Schley
M
M
Petroianu
G A
GA
Schmeck
J
J
Konrad
C
C
D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000201:enzymology*; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D054513:Group IV Phospholipases A2; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2
D000759:Adjuvants, Anesthesia; D000316:Adrenergic alpha-Agonists; D000893:Anti-Inflammatory Agents; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2; D003000:Clonidine