Effects of acute and chronic administration of Leu-enkephalin on cultured serotonergic neurons: evidence for opioids as inhibitory neuronal growth factors

M. I. Davila-Garcia, E. C. Azmitia

Research output: Contribution to journalArticle

Abstract

Leu-enkephalin, at concentrations between 18 μM and 1.8 pM, was administered in a single or daily dose to dissociated mesencephalic raphe cell cultures maintained for 3 or 5 days. Daily administration of Leu-enkephalin produced an inhibition of high affinity uptake of [3H]5-HT, a measure of serotonergic process outgrowth in cultures of fetal neurons. This inhibition was maximal at a dose of 18 nM in both 3 (59%, P < 0.05)- and 5 (38%, P < 0.05)-day cultures. The expression of uptake was consistently lower in 5-day cultures than in 3-day cultures at all concentrations tested. In marked contrast, a single dose of Leu-enkephalin at the time of plating stimulated uptake in 3- and 5-day cultures. Maximal stimulation was observed at 180 nM for both 3 (191%, P < 0.05)- and 5 (140%, P < 0.05)-day cultures. The results obtained after a single dose of the opioid may reflect a paradoxical stimulation probably due to a rebound mechanism of receptors since co-administration of bacitracin (0.5 mg/ml), an aminopeptidase inhibitor, resulted in inhibition of the uptake expression. Together these results indicate that Leu-enkephalin can function as an inhibitory regulatory growth factor for neuronal cultures when constant exposure to this opioid is maintained over time.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalDevelopmental Brain Research
Volume49
Issue number1
DOIs
StatePublished - Sep 1 1989

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Leucine Enkephalin
Serotonergic Neurons
Opioid Analgesics
Bacitracin
Aminopeptidases
Process Assessment (Health Care)
Serotonin
Cell Culture Techniques
Neurons
growth inhibitory factor

Keywords

  • Bacitracin
  • Cell culture
  • Development
  • Leu-enkephalin
  • Rat
  • Receptor
  • Serotonin
  • Uptake

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

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title = "Effects of acute and chronic administration of Leu-enkephalin on cultured serotonergic neurons: evidence for opioids as inhibitory neuronal growth factors",
abstract = "Leu-enkephalin, at concentrations between 18 μM and 1.8 pM, was administered in a single or daily dose to dissociated mesencephalic raphe cell cultures maintained for 3 or 5 days. Daily administration of Leu-enkephalin produced an inhibition of high affinity uptake of [3H]5-HT, a measure of serotonergic process outgrowth in cultures of fetal neurons. This inhibition was maximal at a dose of 18 nM in both 3 (59{\%}, P < 0.05)- and 5 (38{\%}, P < 0.05)-day cultures. The expression of uptake was consistently lower in 5-day cultures than in 3-day cultures at all concentrations tested. In marked contrast, a single dose of Leu-enkephalin at the time of plating stimulated uptake in 3- and 5-day cultures. Maximal stimulation was observed at 180 nM for both 3 (191{\%}, P < 0.05)- and 5 (140{\%}, P < 0.05)-day cultures. The results obtained after a single dose of the opioid may reflect a paradoxical stimulation probably due to a rebound mechanism of receptors since co-administration of bacitracin (0.5 mg/ml), an aminopeptidase inhibitor, resulted in inhibition of the uptake expression. Together these results indicate that Leu-enkephalin can function as an inhibitory regulatory growth factor for neuronal cultures when constant exposure to this opioid is maintained over time.",
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T1 - Effects of acute and chronic administration of Leu-enkephalin on cultured serotonergic neurons

T2 - evidence for opioids as inhibitory neuronal growth factors

AU - Davila-Garcia, M. I.

AU - Azmitia, E. C.

PY - 1989/9/1

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N2 - Leu-enkephalin, at concentrations between 18 μM and 1.8 pM, was administered in a single or daily dose to dissociated mesencephalic raphe cell cultures maintained for 3 or 5 days. Daily administration of Leu-enkephalin produced an inhibition of high affinity uptake of [3H]5-HT, a measure of serotonergic process outgrowth in cultures of fetal neurons. This inhibition was maximal at a dose of 18 nM in both 3 (59%, P < 0.05)- and 5 (38%, P < 0.05)-day cultures. The expression of uptake was consistently lower in 5-day cultures than in 3-day cultures at all concentrations tested. In marked contrast, a single dose of Leu-enkephalin at the time of plating stimulated uptake in 3- and 5-day cultures. Maximal stimulation was observed at 180 nM for both 3 (191%, P < 0.05)- and 5 (140%, P < 0.05)-day cultures. The results obtained after a single dose of the opioid may reflect a paradoxical stimulation probably due to a rebound mechanism of receptors since co-administration of bacitracin (0.5 mg/ml), an aminopeptidase inhibitor, resulted in inhibition of the uptake expression. Together these results indicate that Leu-enkephalin can function as an inhibitory regulatory growth factor for neuronal cultures when constant exposure to this opioid is maintained over time.

AB - Leu-enkephalin, at concentrations between 18 μM and 1.8 pM, was administered in a single or daily dose to dissociated mesencephalic raphe cell cultures maintained for 3 or 5 days. Daily administration of Leu-enkephalin produced an inhibition of high affinity uptake of [3H]5-HT, a measure of serotonergic process outgrowth in cultures of fetal neurons. This inhibition was maximal at a dose of 18 nM in both 3 (59%, P < 0.05)- and 5 (38%, P < 0.05)-day cultures. The expression of uptake was consistently lower in 5-day cultures than in 3-day cultures at all concentrations tested. In marked contrast, a single dose of Leu-enkephalin at the time of plating stimulated uptake in 3- and 5-day cultures. Maximal stimulation was observed at 180 nM for both 3 (191%, P < 0.05)- and 5 (140%, P < 0.05)-day cultures. The results obtained after a single dose of the opioid may reflect a paradoxical stimulation probably due to a rebound mechanism of receptors since co-administration of bacitracin (0.5 mg/ml), an aminopeptidase inhibitor, resulted in inhibition of the uptake expression. Together these results indicate that Leu-enkephalin can function as an inhibitory regulatory growth factor for neuronal cultures when constant exposure to this opioid is maintained over time.

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