Role of guanylyl cyclase activation via thiamine in suppressing chemically-induced writhing in mouse.
The possible role of L-arginine/nitric oxide (L-arginine/NO) pathway in the antinociceptive activity of thiamine (vitamin B1) in p-benzoquinone-induced mouse writhing model was investigated. Thiamine (ED50, 0.11 mg/kg), L-arginine (50 mg/kg), NG-nitro L-arginine methyl ester (L-NAME, 75 mg/kg) and morphine (ED50: 0.13 mg/kg) displayed antinociceptions following s.c. administrations (52.4 +/- 5.5%, 36.8 +/- 7.7%, 27.8 +/- 11.1%, 66.1 +/- 3.5%, respectively). However, methylene blue (MB, 40 mg/kg, s.c.) produced a nociception (-32.1 +/- 9.9%). Coadministration of B1 with L-arginine did not significantly change L-arginine-induced antinociception (48.9 +/- 3.7%). Cotreatment of thiamine with L-NAME and MB significantly increased the L-NAME-induced antinociception (53.9 +/- 3.9%) and reversed the MB-induced nociception to antinociception (46.0 +/- 4.2%). L-Arginine and L-NAME-induced antinociceptions were significantly increased (55.9 +/- 3.9% and 61.1 +/- 5.0%, respectively) by morphine. MB-induced nociception significantly reversed to antinociception by the concomitant administration of morphine (41.6 +/- 8.9%). Thiamine and morphine coadministration displayed antinociception (46.0 +/- 4.2%). The present results suggest that thiamine could produce antinociception by the activation of guanylyl cyclase mediated by cyclic guanosine monophosphate (cGMP) that may trigger the possible involvement of central and/or peripheral L-arginine/NO/cGMP pathway.
Abacioğlu
N
N
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. nabaci@farma.net.tr
Demir
S
S
Cakici
I
I
Tunçtan
B
B
Kanzik
I
I
D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects; D013831:Thiamine / Q000494:pharmacology*
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester; D013831:Thiamine