Calcitonin gene-related peptide (CGRP) in the rat central nervous system

patterns of immunoreactivity and receptor binding sites

Lawrence Kruger, Patrick W Mantyh, Catia Sternini, Nicholas C. Brecha, Christopher R. Mantyh

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

The distribution of immunoreactive (IR) axons and neurons in the rat central nervous system (CNS) has been studied with an antiserum directed against the C-terminal sequence of rat α-calcitonin gene-related peptide (CGRP) and a durable peroxidase reaction product for detailed analysis in relation to normal cytoarchitecture. These materials were studied and illustrated in the three principal axes in relation to cell-stained adjacent sections in normal as well as colchicine- and capsaicin-treated animals, although no fundamental differences in pattern were evident in neurotoxin-treated rats. The patterns of CGRP-IR were then compared with autoradiograms of specific, high affinity receptor binding sites for 125I-human α-CGRP. CGRP-IR labeling in motor systems includes the vast majority of motoneurons, enabling facile identification of isolated 'accessory' populations. Preganglionic parasympathetic nuclei revealed only labeling of a small proportion of neurons. By contrast, the sensory systems revealed a diversity of labeling patterns precluding simple generalizations. Peripheral input ranges from extensive labeling of thin somatic afferents, feeble to moderate gustatory and olfactory afferents to a total absence of auditory afferents, yet IR axons and neurons can be found in selective distribution within each of these sensory systems. Patterns of IR in various integrative centers, e.g. cerebellum, basal ganglia and hypothalamus, reveal selectivity that fails to conform to conventional descriptions of functional systems. Some regions display unexpected patterns, e.g. vertical stripes in cerebellar cortex. CGRP receptor binding sites (RB) are found in many of the sites where IR axons terminate and in some cases, e.g. motor neurons, which express intraneuronal IR. The main sensory systems reveal a variety of RB patterns, only a few of which can be related to sites of IR axon terminals. Many apparent 'mismatches' between IR and RB are illustrated and discussed in the context of functional peptide expression or in quasi-hormonal terms. It is suggested that the principle of CGRP-IR axon distribution in peripheral tissues, where synapses are lacking, might also apply to the CNS and that neither the locus of IR-axon terminals nor RB sites need indicate transmitter action for impulse information transfer. CGRP is a widely distributed neuromodulator probably subserving a role in both synaptic and metabolic regulation, depending on the specific requirements of the diverse distribution of its receptors.

Original languageEnglish (US)
Pages (from-to)223-244
Number of pages22
JournalBrain Research
Volume463
Issue number2
DOIs
StatePublished - Nov 1 1988
Externally publishedYes

Fingerprint

Calcitonin Gene-Related Peptide
Central Nervous System
Binding Sites
Axons
Presynaptic Terminals
Motor Neurons
Neurons
Calcitonin Gene-Related Peptide Receptors
Cerebellar Cortex
Capsaicin
Neurotoxins
Colchicine
Basal Ganglia
Synapses
Cerebellum
Peroxidase
Hypothalamus
Neurotransmitter Agents
Immune Sera
Peptides

Keywords

  • Autonomic system
  • Calcitonin gene-related peptide
  • Immunohistochemistry
  • Motor system
  • Neuropeptide
  • Rat
  • Receptor binding site
  • Sensory system

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Calcitonin gene-related peptide (CGRP) in the rat central nervous system : patterns of immunoreactivity and receptor binding sites. / Kruger, Lawrence; Mantyh, Patrick W; Sternini, Catia; Brecha, Nicholas C.; Mantyh, Christopher R.

In: Brain Research, Vol. 463, No. 2, 01.11.1988, p. 223-244.

Research output: Contribution to journalArticle

Kruger, Lawrence ; Mantyh, Patrick W ; Sternini, Catia ; Brecha, Nicholas C. ; Mantyh, Christopher R. / Calcitonin gene-related peptide (CGRP) in the rat central nervous system : patterns of immunoreactivity and receptor binding sites. In: Brain Research. 1988 ; Vol. 463, No. 2. pp. 223-244.
@article{065acc3772644af980c95613f9acc8a1,
title = "Calcitonin gene-related peptide (CGRP) in the rat central nervous system: patterns of immunoreactivity and receptor binding sites",
abstract = "The distribution of immunoreactive (IR) axons and neurons in the rat central nervous system (CNS) has been studied with an antiserum directed against the C-terminal sequence of rat α-calcitonin gene-related peptide (CGRP) and a durable peroxidase reaction product for detailed analysis in relation to normal cytoarchitecture. These materials were studied and illustrated in the three principal axes in relation to cell-stained adjacent sections in normal as well as colchicine- and capsaicin-treated animals, although no fundamental differences in pattern were evident in neurotoxin-treated rats. The patterns of CGRP-IR were then compared with autoradiograms of specific, high affinity receptor binding sites for 125I-human α-CGRP. CGRP-IR labeling in motor systems includes the vast majority of motoneurons, enabling facile identification of isolated 'accessory' populations. Preganglionic parasympathetic nuclei revealed only labeling of a small proportion of neurons. By contrast, the sensory systems revealed a diversity of labeling patterns precluding simple generalizations. Peripheral input ranges from extensive labeling of thin somatic afferents, feeble to moderate gustatory and olfactory afferents to a total absence of auditory afferents, yet IR axons and neurons can be found in selective distribution within each of these sensory systems. Patterns of IR in various integrative centers, e.g. cerebellum, basal ganglia and hypothalamus, reveal selectivity that fails to conform to conventional descriptions of functional systems. Some regions display unexpected patterns, e.g. vertical stripes in cerebellar cortex. CGRP receptor binding sites (RB) are found in many of the sites where IR axons terminate and in some cases, e.g. motor neurons, which express intraneuronal IR. The main sensory systems reveal a variety of RB patterns, only a few of which can be related to sites of IR axon terminals. Many apparent 'mismatches' between IR and RB are illustrated and discussed in the context of functional peptide expression or in quasi-hormonal terms. It is suggested that the principle of CGRP-IR axon distribution in peripheral tissues, where synapses are lacking, might also apply to the CNS and that neither the locus of IR-axon terminals nor RB sites need indicate transmitter action for impulse information transfer. CGRP is a widely distributed neuromodulator probably subserving a role in both synaptic and metabolic regulation, depending on the specific requirements of the diverse distribution of its receptors.",
keywords = "Autonomic system, Calcitonin gene-related peptide, Immunohistochemistry, Motor system, Neuropeptide, Rat, Receptor binding site, Sensory system",
author = "Lawrence Kruger and Mantyh, {Patrick W} and Catia Sternini and Brecha, {Nicholas C.} and Mantyh, {Christopher R.}",
year = "1988",
month = "11",
day = "1",
doi = "10.1016/0006-8993(88)90395-2",
language = "English (US)",
volume = "463",
pages = "223--244",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Calcitonin gene-related peptide (CGRP) in the rat central nervous system

T2 - patterns of immunoreactivity and receptor binding sites

AU - Kruger, Lawrence

AU - Mantyh, Patrick W

AU - Sternini, Catia

AU - Brecha, Nicholas C.

AU - Mantyh, Christopher R.

PY - 1988/11/1

Y1 - 1988/11/1

N2 - The distribution of immunoreactive (IR) axons and neurons in the rat central nervous system (CNS) has been studied with an antiserum directed against the C-terminal sequence of rat α-calcitonin gene-related peptide (CGRP) and a durable peroxidase reaction product for detailed analysis in relation to normal cytoarchitecture. These materials were studied and illustrated in the three principal axes in relation to cell-stained adjacent sections in normal as well as colchicine- and capsaicin-treated animals, although no fundamental differences in pattern were evident in neurotoxin-treated rats. The patterns of CGRP-IR were then compared with autoradiograms of specific, high affinity receptor binding sites for 125I-human α-CGRP. CGRP-IR labeling in motor systems includes the vast majority of motoneurons, enabling facile identification of isolated 'accessory' populations. Preganglionic parasympathetic nuclei revealed only labeling of a small proportion of neurons. By contrast, the sensory systems revealed a diversity of labeling patterns precluding simple generalizations. Peripheral input ranges from extensive labeling of thin somatic afferents, feeble to moderate gustatory and olfactory afferents to a total absence of auditory afferents, yet IR axons and neurons can be found in selective distribution within each of these sensory systems. Patterns of IR in various integrative centers, e.g. cerebellum, basal ganglia and hypothalamus, reveal selectivity that fails to conform to conventional descriptions of functional systems. Some regions display unexpected patterns, e.g. vertical stripes in cerebellar cortex. CGRP receptor binding sites (RB) are found in many of the sites where IR axons terminate and in some cases, e.g. motor neurons, which express intraneuronal IR. The main sensory systems reveal a variety of RB patterns, only a few of which can be related to sites of IR axon terminals. Many apparent 'mismatches' between IR and RB are illustrated and discussed in the context of functional peptide expression or in quasi-hormonal terms. It is suggested that the principle of CGRP-IR axon distribution in peripheral tissues, where synapses are lacking, might also apply to the CNS and that neither the locus of IR-axon terminals nor RB sites need indicate transmitter action for impulse information transfer. CGRP is a widely distributed neuromodulator probably subserving a role in both synaptic and metabolic regulation, depending on the specific requirements of the diverse distribution of its receptors.

AB - The distribution of immunoreactive (IR) axons and neurons in the rat central nervous system (CNS) has been studied with an antiserum directed against the C-terminal sequence of rat α-calcitonin gene-related peptide (CGRP) and a durable peroxidase reaction product for detailed analysis in relation to normal cytoarchitecture. These materials were studied and illustrated in the three principal axes in relation to cell-stained adjacent sections in normal as well as colchicine- and capsaicin-treated animals, although no fundamental differences in pattern were evident in neurotoxin-treated rats. The patterns of CGRP-IR were then compared with autoradiograms of specific, high affinity receptor binding sites for 125I-human α-CGRP. CGRP-IR labeling in motor systems includes the vast majority of motoneurons, enabling facile identification of isolated 'accessory' populations. Preganglionic parasympathetic nuclei revealed only labeling of a small proportion of neurons. By contrast, the sensory systems revealed a diversity of labeling patterns precluding simple generalizations. Peripheral input ranges from extensive labeling of thin somatic afferents, feeble to moderate gustatory and olfactory afferents to a total absence of auditory afferents, yet IR axons and neurons can be found in selective distribution within each of these sensory systems. Patterns of IR in various integrative centers, e.g. cerebellum, basal ganglia and hypothalamus, reveal selectivity that fails to conform to conventional descriptions of functional systems. Some regions display unexpected patterns, e.g. vertical stripes in cerebellar cortex. CGRP receptor binding sites (RB) are found in many of the sites where IR axons terminate and in some cases, e.g. motor neurons, which express intraneuronal IR. The main sensory systems reveal a variety of RB patterns, only a few of which can be related to sites of IR axon terminals. Many apparent 'mismatches' between IR and RB are illustrated and discussed in the context of functional peptide expression or in quasi-hormonal terms. It is suggested that the principle of CGRP-IR axon distribution in peripheral tissues, where synapses are lacking, might also apply to the CNS and that neither the locus of IR-axon terminals nor RB sites need indicate transmitter action for impulse information transfer. CGRP is a widely distributed neuromodulator probably subserving a role in both synaptic and metabolic regulation, depending on the specific requirements of the diverse distribution of its receptors.

KW - Autonomic system

KW - Calcitonin gene-related peptide

KW - Immunohistochemistry

KW - Motor system

KW - Neuropeptide

KW - Rat

KW - Receptor binding site

KW - Sensory system

UR - http://www.scopus.com/inward/record.url?scp=0023715267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023715267&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(88)90395-2

DO - 10.1016/0006-8993(88)90395-2

M3 - Article

VL - 463

SP - 223

EP - 244

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -