Flurbiprofen inhibits capsaicin induced calcitonin gene related peptide release from rat spinal cord via an endocannabinoid dependent mechanism.
Calcitonin gene related peptide (CGRP) is involved in nociceptive transmission and modulation at the spinal level. In the spinal superperfusion model, Delta(9) tetrahydrocannabinol inhibited capsaicin induced CGRP release in a concentration dependent manner. Similarly, flurbiprofen (3 microM) inhibited spinal CGRP release. This inhibition was reversed by the CB(1) antagonist AM-251 (1 microM), but not by co-administration of prostaglandin E(2) (PGE(2); 285 nM). AM-251 had no modulatory effect on flurbiprofen-induced cyclooxygenase (COX) inhibiting capacity as shown by PGE(2) levels. Furthermore, the phospholipase A(2) inhibitor palmityl trifluromethyl ketone (15 microM) reversed flurbiprofen's inhibitory effect. In conclusion the present work provides evidence on the shift of arachidonic acid metabolism towards endocannabinoids formation in response to COX inhibition as a mechanism for flurbiprofen inhibitory effect on spinal CGRP release.
Seidel
Kay
K
Department of Experimental and Clinical Pharmacology and Toxicology, University Erlangen-Nürnberg Fahrstrasse 17, D-91054, Erlangen, Germany.
Hamza
May
M
Ates
Mehmet
M
Gühring
Hans
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D063385:Cannabinoid Receptor Modulators; D002211:Capsaicin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005480:Flurbiprofen / Q000494:pharmacology*; D007118:Immunoassay; D066298:In Vitro Techniques; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D063385:Cannabinoid Receptor Modulators; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C103505:AM 251; D005480:Flurbiprofen; D013759:Dronabinol; D010741:Phospholipases A; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D002211:Capsaicin