Dopamine dependent decrease in enkephalin and substance P levels in basal ganglia regions of postmortem Parkinsonian brains

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Abstract

This study examined whether a relationship exists between the degree of dopamine (DA) loss and the changes in opioid (Met5-enkephalin, ME; dynorphin A (1-8) (DYN)) or tachykinin (substance P, SP) peptidergic systems in basal ganglia (caudate and putamen) and limbic (frontal cortex) regions of postmortem tissue samples derived from patients who died of Parkinson's disease (PD). The levels of ME, SP and DYN were determined by radioimmunoassays. The levels of DA and 5-hydroxytryptamine (5-HT) and their metabolites were determined by HPLC with electrochemical detection. The degree of loss of DA in PD tissues was classified into two major categories, those with less than 80% and those with more than 80% loss as compared to control. The results reveals that only the category with greater than 80% DA loss exhibited lower levels of ME in caudate and SP in putamen whereas no differences were observed in the levels of DYN in these regions. The frontal cortical region exhibited no changes in the levels of peptides. In other studies, experimental DA deficiency in rodents induced by neurotoxin such as 6-hydroxydopamine (6-OHDA) produced an increase in ME and a decrease in SP in basal ganglia. However, the levels of both peptides were lower in postmortem Parkinsonian basal ganglia in the present study. It appears that there is a DA-dependent, secondary loss of enkephalin and tachykinin peptides in PD. In view of the involvement of these peptidergic systems in the regulation of behaviour, movement, memory and other functions, derangements in these systems should be considered as additional factors in the progression of symptoms of PD.

Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalNeuropeptides
Volume18
Issue number4
DOIs
StatePublished - 1991

Fingerprint

Enkephalins
Substance P
Basal Ganglia
Dopamine
Brain
Parkinson Disease
Tachykinins
dynorphin (1-8)
Oxidopamine
Putamen
Peptides
Tissue
Neurotoxins
Frontal Lobe
Metabolites
Opioid Analgesics
Radioimmunoassay
Rodentia
Serotonin
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Clinical Neurology
  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

Cite this

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title = "Dopamine dependent decrease in enkephalin and substance P levels in basal ganglia regions of postmortem Parkinsonian brains",
abstract = "This study examined whether a relationship exists between the degree of dopamine (DA) loss and the changes in opioid (Met5-enkephalin, ME; dynorphin A (1-8) (DYN)) or tachykinin (substance P, SP) peptidergic systems in basal ganglia (caudate and putamen) and limbic (frontal cortex) regions of postmortem tissue samples derived from patients who died of Parkinson's disease (PD). The levels of ME, SP and DYN were determined by radioimmunoassays. The levels of DA and 5-hydroxytryptamine (5-HT) and their metabolites were determined by HPLC with electrochemical detection. The degree of loss of DA in PD tissues was classified into two major categories, those with less than 80{\%} and those with more than 80{\%} loss as compared to control. The results reveals that only the category with greater than 80{\%} DA loss exhibited lower levels of ME in caudate and SP in putamen whereas no differences were observed in the levels of DYN in these regions. The frontal cortical region exhibited no changes in the levels of peptides. In other studies, experimental DA deficiency in rodents induced by neurotoxin such as 6-hydroxydopamine (6-OHDA) produced an increase in ME and a decrease in SP in basal ganglia. However, the levels of both peptides were lower in postmortem Parkinsonian basal ganglia in the present study. It appears that there is a DA-dependent, secondary loss of enkephalin and tachykinin peptides in PD. In view of the involvement of these peptidergic systems in the regulation of behaviour, movement, memory and other functions, derangements in these systems should be considered as additional factors in the progression of symptoms of PD.",
author = "Subbiah Sivam",
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