Dynorphin-mediated antinociceptive effects of L-arginine and SIN-1 (an NO donor) in mice.
The antinociceptive response of mice to the amino acid L-arginine (L-ARG) has been attributed to either an opioid mechanism or a non-opioid but nitric oxide (NO)-dependent mechanism. Earlier it was reported that the mechanism of nitrous oxide-induced antinociception involved opioid components and was also dependent on brain NO. This study was designed to determine whether the antinociceptive effects of L-ARG and the NO donor 3-morpholinosydnoimine (SIN-1) might be mediated by brain mechanisms similar to those that are responsible for nitrous oxide (N(2)O) antinociception. L-ARG and SIN-1 were administered to mice intracerebroventricularly (i.c.v.), and antinociception was assessed using the acetic acid abdominal constriction test. Both L-ARG and SIN-1 caused dose-related antinociceptive effects that were blocked by naloxone and norbinaltorphimine. The antinociceptive effects of both SIN-1 and L-ARG were also blocked to a greater extent by i.c.v. administration of a rabbit antiserum against rat dynorphin 1-13 than an antiserum against methionine-enkephalin, suggesting that the SIN-1 and L-ARG effects may be related to stimulated release of dynorphin. The antinociceptive effect of L-ARG was antagonized by an inhibitor of neuoronal NO synthase enzyme, indicating that L-ARG had to be converted to NO for its antinociceptive action. These findings indicate that the mechanisms of antinociceptive action of L-ARG and SIN-1 are both mediated by dynorphin and dependent on NO.
Chung
Eunhee
E
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, P.O. Box 646534, Pullman, 99164-6534, USA.
Burke
Brianna
B
Bieber
Andrew J
AJ
Doss
Jason C
JC
Ohgami
Yusuke
Y
Quock
Raymond M
RM
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects*; D004399:Dynorphins / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D010147:Pain Measurement
D000700:Analgesics; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D020030:Nitric Oxide Donors; D009270:Naloxone; C002385:linsidomine; D004399:Dynorphins; D001120:Arginine; D008981:Molsidomine