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-Ala(2),D-Leu(5)-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-Ala(2)-MePhe(4),Gly-ol(5)-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.

High opioid doses inhibit whereas low doses enhance neuritogenesis in PC12 cells / B. Tenconi, E. Lesma, A. Di Giulio, A. Gorio. - In: BRAIN RESEARCH. DEVELOPMENTAL BRAIN RESEARCH.. - ISSN 0165-3806. - 94:2(1996), pp. 175-181.

High opioid doses inhibit whereas low doses enhance neuritogenesis in PC12 cells

E. Lesma
Secondo
;
A. Di Giulio
Penultimo
;
A. Gorio
Ultimo
1996

Abstract

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-Ala(2),D-Leu(5)-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-Ala(2)-MePhe(4),Gly-ol(5)-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.
Morphine; Nerve growth factor; Neuritogenesis; Opioid receptors; Regeneration
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/184853
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