title: Increasing the availability of l-arginine and nitric oxide increases sensitivity of nitrous oxide (N2O)-insensitive inbred mice to N2O-induced antinociception.
abstract: Nitrous oxide (N2O)-induced antinociception in mice is dependent on the neuromodulator nitric oxide (NO). In contrast to C57BL/6J (B6) mice, DBA/2J (D2) mice fail to respond to N2O with a robust antinociceptive response or with an increase in brain nitric oxide synthase (NOS) enzyme activity, suggesting that failure of D2 mice to respond to N2O might result from a deficit of NO function. Therefore, it was of interest to determine whether increasing the availability of NO might increase sensitivity of D2 mice to N2O. Male D2 mice were pretreated with sub-antinociceptive intracerebroventricular doses of the NO donor 3-morpholinosydnoimine or the NO precursor l-arginine then assessed for responsiveness to N2O-induced antinociception using the acetic acid abdominal constriction test. Both pretreatments increased the antinociceptive responsiveness of D2 mice to N2O. These results indicate that the NOS enzyme in D2 mice is functional and that the deficit in NO function that obstructs sensitivity to N2O-induced antinociception may lie in availability or utilization of l-arginine.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164, United States.
authors: Eunhee
authors: E
authors: Chung
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164, United States.
authors: Yusuke
authors: Y
authors: Ohgami
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164, United States. Electronic address: quock@wsu.edu.
authors: Raymond M
authors: RM
authors: Quock
mesh_terms: D015746:Abdominal Pain / Q000150:complications / Q000188:drug therapy*; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009609:Nitrous Oxide / Q000627:therapeutic use*; D017288:Pain Threshold / Q000187:drug effects*; D013045:Species Specificity
chemical_list: D000700:Analgesics; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D009609:Nitrous Oxide
keywords: Antinociception; Inbred mouse strains; NO donor; Nitrous oxide; l-Arginine