High opioid doses inhibit whereas low doses enhance neuritogenesis in PC12 cells.
Exposure to opiates affects brain development, cell growth as well as in vitro cell differentiation [33,34]. Perinatal treatment with morphine has been reported to impair neuronal plasticity after neonatal lesion with 5,7-dihydroxytryptamine (5,7-DHT) [8]. This study has investigated the use of mu, delta and kappa opioid receptor ligands to examine the selective receptor mediated inhibition of PC12 neurite formation. Morphine and D-Ala2,D-Leu5-enkephalin (DADLE) had a comparable inhibitory potency with a maximal effect at 1 mM concentration, while both naltrexone and naltrindole antagonized their effect at only 10 nM. D-Ala2-MePhe4,Gly-ol5-enkephalin (DAMGO) showed only a transient inhibitory effect. The administration of 10 nM guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) prevented morphine inhibition. It is suggested that opiate inhibition of neuritogenesis may be mediated by a receptor with delta-like characteristics coupled to G proteins. On the other hand, the activation of this receptor with morphine at a very low concentration (1 pM) actually enhanced nerve growth factor (NGF) neurite promoting activity.
Tenconi
B
B
Department of Medical Pharmacology, University of Milan, Italy.
Lesma
E
E
DiGiulio
A M
AM
Gorio
A
A
D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors
D009294:Narcotics; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009020:Morphine; D019204:GTP-Binding Proteins