Twenty-four-hour variation of L-arginine/nitric oxide/cyclic guanosine monophosphate pathway demonstrated by the mouse visceral pain model.
The L-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway is known to be involved in central and peripheral nociceptive processes. This study evaluated the rhythmic pattern of the L-arginine/NO/cGMP pathway using the mouse visceral pain model. Experiments were performed at six different times (1, 5, 9, 13, 17, and 21 h after light on) per day in male mice synchronized to a 12 h:12 h light-dark cycle. Animals were injected s.c. with saline, 2 mg/kg L-arginine (a NO precursor), 75 mg/kg L-N(G)-nitroarginine methyl ester (L-NAME, a NOS inhibitor), 40 mg/kg methylene blue (a soluble guanylyl cyclase and/or NOS inhibitor), or 0.1 mg/kg sodium nitroprusside (a nonenzymatic NO donor) 15 min before counting 2.5 mg/kg (i.p.) p-benzoquinone (PBQ)-induced abdominal constrictions for 15 min. Blood samples were collected after the test, and the nitrite concentration was determined in serum samples. L-arginine or L-NAME caused both antinociception and nociception, depending on the circadian time of their injection. The analgesic effect of methylene blue or sodium nitroprusside exhibited significant biological time-dependent differences in PBQ-induced abdominal constrictions. Serum nitrite levels also displayed a significant 24 h variation in mice injected with PBQ, L-NAME, methylene blue, or sodium nitroprusside, but not saline or L-arginine. These results suggest that components of L-arginine/NO/cGMP pathway exhibit biological time-dependent effects on visceral nociceptive process.
Uludag
Orhan
O
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Tunctan
Bahar
B
Altug
Sedat
S
Zengil
Hakan
H
Abacioglu
Nurettin
N
D015746:Abdominal Pain / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D016227:Benzoquinones / Q000633:toxicity; D002940:Circadian Rhythm / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000097:blood; D009599:Nitroprusside / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009573:Nitrites; D009599:Nitroprusside; D009569:Nitric Oxide; C004532:quinone; D001120:Arginine; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester