Airway smooth muscle relaxations induced by dipyrone.
BACKGROUND
Dipyrone differs from other nonsteroidal anti-inflammatory drugs with a distinctive spasmolytic effect; however, the mechanism of action is not clear yet. The possible mechanism behind this effect was investigated on airway smooth muscle tone in vitro.


METHODS
The effect of dipyrone on inositol phosphate (IP) accumulation was evaluated on guinea pig trachea smooth muscle. Changes in intracellular free calcium levels and IP accumulation were evaluated in LTK8 cells.


RESULTS
Dipyrone (0.01, 0.1, 1 mmol/l) had a relaxing effect on histamine (0.02 mmol/l)- and adenosine triphosphate- (ATP) (0.01 mol/l)-induced contractions, but not potassium chloride (KCl)-stimulated contractions. This relaxing effect was not observed with indomethacin. Indomethacin did not inhibit the relaxation response of dipyrone. In isolated tracheal smooth muscle, histamine- (0.02 mmol/l) and ATP (0.01 mmol/l)-induced IP accumulation was significantly inhibited by dipyrone (1 mmol/l). ATP (0.01 mmol/l)-induced IP accumulation was also significantly inhibited by dipyrone (0.01 mmol/l) in LTK8 cells. Dipyrone inhibited ATP-induced (0.01 and 0.1 mmol/l) intracellular calcium increase in LTK8 cells.


CONCLUSIONS
Inhibition of the release of intracellular Ca(2+) may play a role in the smooth muscle relaxing effect of dipyrone. The inhibitor effect of dipyrone on IP accumulation may be due to direct inhibition of phospholipase C (PLC) or impairment of the activation of PLC by G protein-coupled receptor (GPCR).
Gulmez
S Ezgi
SE
Department of Pharmacology and Clinical Pharmacology, Ankara University Faculty of Medicine, Sihhiye, Ankara, Turkey. gulmez@medicine.ankara.edu.tr
Gurdal
Hakan
H
Tulunay
F Cankat
FC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004177:Dipyrone / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000737:chemistry*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D004177:Dipyrone; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2