The role of L-arginine/nitric oxide pathway in the antinociceptive activity of pyridoxine in mouse.
In the present study the role of L-arginine/nitric oxide (NO)/cGMP pathway in the antinociceptive activity of pyridoxine in p-benzoquinone-induced abdominal constriction test in mouse was investigated. Pyridoxine (CAS 58-56-0) displayed dose-dependent antinociceptive activity at 0.0625-1 mg/kg (s.c.) doses. L-arginine (CAS 1119-34-2), a NO precursor, displayed a triphasic pattern as antinociception-nociception-antinociception (61.8 +/- 7.8, -36.5 +/- 12.7 and 17.0 +/- 4.3%, 5, 40 and 50 mg/kg, s.c., respectively). The antinociceptive effect of pyridoxine at ED50 dose (0.43 mg/kg, s.c.) (47.7 +/- 3.9%) was significantly decreased by L-arginine at 40 and 50 mg/kg doses (4.1 +/- 9.3 and 37.8 +/- 1.6%, respectively) while 5 mg/kg dose of L-arginine significantly potentiated the pyridoxine analgesia. On the other hand, pyridoxine reversed the L-arginine-induced nociception to antinociception (4.1 +/- 9.3%) and augmented the antinociceptive effect of L-arginine (37.8 +/- 1.6%). L-NG-nitroarginine methyl ester (CAS 51298-62-5), a NO synthase inhibitor, at 75 mg/kg, s.c. produced antinociception and significantly increased the antinociceptive effect of pyridoxine (63.7 +/- 1.2%). Methylene blue (CAS 61-73-4, MB), a guanylyl cyclase and/or NO synthase inhibitor, was antinociceptive and nociceptive at 5 and 40 mg/kg doses, respectively, 5 mg/kg dose of MB significantly increased the antinociceptive effect of pyridoxine, but did not change it at 40 mg/kg dose. On the other hand, pyridoxine significantly decreased the antinociceptive effect of MB and reversed the MB-induced nociception to antinociception. Combination of pyridoxine and morphine (CAS 57-27-2) (ED50: 0.13 mg/kg, s.c.) at 49.8 +/- 1.9% revealed a significant antinociceptive potentiation (69.1 +/- 1.8%). The findings of the present study emphasise the contribution of central and/or peripheral L-arginine/NO/cGMP nociceptive processes in pyridoxine-induced antinociception.
Abacioğlu
N
N
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. nabaci@farma.net.tr
Tunçtan
B
B
Cakici
I
I
Akbulut
E
E
Uludağ
O
O
Kanzik
I
I
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue; 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; D011736:Pyridoxine / Q000494:pharmacology*; D025101:Vitamin B 6 / Q000378:metabolism
D000700:Analgesics; D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009020:Morphine; D025101:Vitamin B 6; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D011736:Pyridoxine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester