Effect of chronic morphine treatment on the biosynthesis of agmatine in rat brain and other tissues.
Agmatine is an endogenous amine derived from the decarboxylation of arginine by arginine decarboxylase (ADC), and metabolized to putrescine by agmatinase. Exogenously administered agmatine has several biological actions including its ability to potentiate morphine analgesia and block symptoms of morphine tolerance/withdrawal in rats. To investigate the role of endogenous agmatine in this action, we sought to determine whether chronic exposure to morphine and induction of withdrawal modulate the synthesis of agmatine in rat brain and other tissues. Exposure of rats to morphine for three days significantly decreases the activity of ADC and the levels of agmatine in rat liver, kidney, brain, aorta and intestine with no changes in agmatinase activity. The precipitation of withdrawal syndrome by injecting naloxone further decreases ADC activity and agmatine levels in these tissues. We conclude that endogenous agmatine may play an important role in regulating morphine tolerance/dependence and withdrawal symptoms.
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411, East 69th Street, New York, NY 10021, USA.
Feyza
F
Aricioglu-Kartal
Soundar
S
Regunathan
D000376:Agmatine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002262:Carboxy-Lyases / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; D009270:Naloxone; D000376:Agmatine; D009020:Morphine; D002262:Carboxy-Lyases; C019722:arginine decarboxylase