Tachykinin systems in the spinal cord and basal ganglia

Influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA

Subbiah Sivam, J. E. Krause

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered. Neonatal dopaminergic denervation or haloperidol blockade of dopamine receptors in adult rats decreased PPT mRNA levels in the striatum as previously reported but did not alter the abundance of SPR mRNA in the striatum or substantia nigra. The presence of SPR mRNA levels in microdissected substantia nigra and the lack of alteration in its levels as a consequence of dopamine denervation suggest that the receptor is expressed within nondopaminergic neurons, possibly GABAergic neurons. In both spinal cord and basal ganglia systems, regardless of increases or decreases in SP or SP-encoding mRNA levels, SPR mRNA levels were not altered. We conclude that the regulation of the presynaptic biosynthesis of SP and the postsynaptic regulation of the SPR mRNA can be modulated independently of each other in spinal cord and basal ganglia SP systems.

Original languageEnglish
Pages (from-to)2278-2284
Number of pages7
JournalJournal of Neurochemistry
Volume59
Issue number6
StatePublished - Dec 1992

Fingerprint

Neurokinin-1 Receptors
Tachykinins
Capsaicin
Spinal Ganglia
Substance P
Basal Ganglia
Spinal Cord
Messenger RNA
Peptides
Neurons
Substantia Nigra
Neurokinin A
dynorphin (1-8)
Denervation
Haloperidol
peptide P
Afferent Neurons
GABAergic Neurons
Opioid Peptides
Enkephalins

Keywords

  • 6 - Hydroxydopamine
  • Basal gangli
  • Capsaicin
  • Preprotachykinin
  • Spinal cord
  • Substance P
  • Tachykinin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Tachykinin systems in the spinal cord and basal ganglia: Influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA",
abstract = "The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered. Neonatal dopaminergic denervation or haloperidol blockade of dopamine receptors in adult rats decreased PPT mRNA levels in the striatum as previously reported but did not alter the abundance of SPR mRNA in the striatum or substantia nigra. The presence of SPR mRNA levels in microdissected substantia nigra and the lack of alteration in its levels as a consequence of dopamine denervation suggest that the receptor is expressed within nondopaminergic neurons, possibly GABAergic neurons. In both spinal cord and basal ganglia systems, regardless of increases or decreases in SP or SP-encoding mRNA levels, SPR mRNA levels were not altered. We conclude that the regulation of the presynaptic biosynthesis of SP and the postsynaptic regulation of the SPR mRNA can be modulated independently of each other in spinal cord and basal ganglia SP systems.",
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T1 - Tachykinin systems in the spinal cord and basal ganglia

T2 - Influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA

AU - Sivam, Subbiah

AU - Krause, J. E.

PY - 1992/12

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N2 - The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered. Neonatal dopaminergic denervation or haloperidol blockade of dopamine receptors in adult rats decreased PPT mRNA levels in the striatum as previously reported but did not alter the abundance of SPR mRNA in the striatum or substantia nigra. The presence of SPR mRNA levels in microdissected substantia nigra and the lack of alteration in its levels as a consequence of dopamine denervation suggest that the receptor is expressed within nondopaminergic neurons, possibly GABAergic neurons. In both spinal cord and basal ganglia systems, regardless of increases or decreases in SP or SP-encoding mRNA levels, SPR mRNA levels were not altered. We conclude that the regulation of the presynaptic biosynthesis of SP and the postsynaptic regulation of the SPR mRNA can be modulated independently of each other in spinal cord and basal ganglia SP systems.

AB - The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered. Neonatal dopaminergic denervation or haloperidol blockade of dopamine receptors in adult rats decreased PPT mRNA levels in the striatum as previously reported but did not alter the abundance of SPR mRNA in the striatum or substantia nigra. The presence of SPR mRNA levels in microdissected substantia nigra and the lack of alteration in its levels as a consequence of dopamine denervation suggest that the receptor is expressed within nondopaminergic neurons, possibly GABAergic neurons. In both spinal cord and basal ganglia systems, regardless of increases or decreases in SP or SP-encoding mRNA levels, SPR mRNA levels were not altered. We conclude that the regulation of the presynaptic biosynthesis of SP and the postsynaptic regulation of the SPR mRNA can be modulated independently of each other in spinal cord and basal ganglia SP systems.

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