Role of the nitric-oxide synthase isoforms during morphine-induced hyperthermia in rats.
Recently, we demonstrated that the diffusible messenger molecule nitric oxide (NO) is involved in the hyperthermic response induced by morphine by using a nonselective nitric-oxide synthase inhibitor, N-nitro-L-arginine methyl ester. The present work extended these studies to include 7-nitroindazole (7-NI), an inhibitor specific for neuronal nitric-oxide synthase (nNOS), N(5)-(-iminoethyl)-L-ornithine (L-NIO), an inhibitor of endothelial NOS (eNOS), and aminoguanidine (AG), a potent inhibitor of inducible NOS (iNOS). A biotelemetry system was used in this study to measure the body temperature (Tb). A dose of 7-NI (5 or 10 mg/kg), which did not affect Tb by itself, blocked the hyperthermia induced by morphine in a dose-dependent manner (15 mg/kg i.p.). However, pretreatment with L-NIO (10-20 mg/kg) or with AG (50 mg/kg) failed to alter the hyperthermia induced by morphine. L-NIO (10-20 mg/kg) or AG (50 mg/kg) had no effect on Tb. These results suggest the involvement of nNOS in morphine-induced hyperthermia.
Benamar
Khalid
K
Center for Substance Abuse Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA. kabenamar@hotmail.com
Yondorf
Menachem Z
MZ
Kon
David
D
Geller
Ellen B
EB
Adler
Martin W
MW
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000201:enzymology*; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007263:Infusions, Parenteral; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D007527:Isoenzymes; C065027:N(G)-iminoethylornithine; D009020:Morphine; D009952:Ornithine; D019001:Nitric Oxide Synthase; C004479:pimagedine; C080122:7-nitroindazole