Influence of agmatine in adaptation of cAMP signal transduction system of opiate receptors.
OBJECTIVE
To observe attenuative effects of agmatine on opiate desensitization and substance dependence.


METHODS
Guanosine 5'-O-(3-[35S] thiotriphosphate) ([35S]GTTP) binding and cellular cyclic AMP (cAMP) level were determined by radioligand binding assay and radioimmunoassay in NG108-15 cells, respectively.


RESULTS
Agmatine increased stimulative action of opioids on [35S]GTTP binding by about 35% and inhibitory effects of opioids on cellular cAMP concentration by about 114.3% in NG108-15 cells pretreated with opioids. On the other hand, it also inhibited cAMP over-shooting by 214.9% of morphine substance dependent cells precipitated by naloxone compared with that of control. These effects of agmatine were antagonized by idazoxan in a concentration-dependent manner.


CONCLUSIONS
Agmatine reversed the formative process of adaptation in cAMP signal transduction cascade.
Li
J
J
Institute of Pharmacology and Toxicology, Academy of Millitary Medical Sciences, Beijing, China. qinby@nic.bmi.ac.cn
Li
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Pei
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Qin
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BY
D000222:Adaptation, Physiological; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005910:Glioma / Q000473:pathology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006822:Hybrid Cells; D019329:Idazoxan / Q000494:pharmacology; D054755:Imidazoline Receptors; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009447:Neuroblastoma / Q000473:pathology; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000376:Agmatine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D000242:Cyclic AMP; D019329:Idazoxan