Selective distribution of μ-opioid receptors in C1 adrenergic neurons and their afferents

Dennis M. Higgs, Gail D Burd

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Agonists of the μ-opioid receptor (MOR) have profound effects on blood pressure, heart rate, and respiration that may be mediated by C1 adrenergic neurons in the rostral ventrolateral medulla (RVL). C1 neurons are sympathoexcitatory and are involved in both tonic and reflex regulation of sympathetic outflow. This study was designed to determine whether C1 neurons, or their afferents, contain MOR. C1 neurons were identified by using an antibody against the epinephrine synthesizing enzyme phenylethanolamine-N-methyl transferase (PNMT), whereas MOR was localized by using an antipeptide antibody that recognizes the cloned MOR, MOR1. Combined immunoperoxidase and immunogold methods were used to examine the cellular distribution of MOR1 relative to PNMT-containing neurons in the RVL. MOR1 was found in 22% of PNMT-containing dendrites (n = 392), whereas MOR1-containing axons or axon terminals contacted 14% of PNMT-containing dendrites. This distribution was heterogenous with regard to dendritic size: PNMT-labeled dendrites containing MOR1 were usually large (60% were >1.2 μm), whereas PNMT-containing dendrites that received MOR1-labeled afferents were usually small (79% were <1.2 μm). Individual dendrites rarely contained MOR1 at both pre- and postsynaptic sites. Together these results suggest that MOR agonists may directly influence the activity of C1 neurons, as well as the activity of select afferents to these cells. Plasmalemmal membrane labeling for MOR1 was more frequent in smaller PNMT-containing dendrites, suggesting that postsynaptic receptors are more readily available for ligand binding in small dendrites, although the receptor was more frequently detected in larger PNMT dendrites. The selective distribution of MORs to specific pre- and postsynaptic sites suggests the receptor may be selectively trafficked to positions where it may regulate afferent activity that is heterogeneously distributed along the dendritic tree of C1 neurons.

Original languageEnglish (US)
Pages (from-to)23-33
Number of pages11
JournalJournal of Comparative Neurology
Volume433
Issue number1
DOIs
StatePublished - Apr 23 2001

Fingerprint

Adrenergic Neurons
Opioid Receptors
Transferases
Dendrites
Neurons
N-phenylethanolamine
Antibodies
Presynaptic Terminals
Epinephrine
Axons
Reflex
Respiration
Heart Rate
Blood Pressure
Ligands
Membranes
Enzymes

Keywords

  • Blood pressure
  • Rostral ventrolateral medulla
  • Ultrastructure

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Selective distribution of μ-opioid receptors in C1 adrenergic neurons and their afferents. / Higgs, Dennis M.; Burd, Gail D.

In: Journal of Comparative Neurology, Vol. 433, No. 1, 23.04.2001, p. 23-33.

Research output: Contribution to journalArticle

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abstract = "Agonists of the μ-opioid receptor (MOR) have profound effects on blood pressure, heart rate, and respiration that may be mediated by C1 adrenergic neurons in the rostral ventrolateral medulla (RVL). C1 neurons are sympathoexcitatory and are involved in both tonic and reflex regulation of sympathetic outflow. This study was designed to determine whether C1 neurons, or their afferents, contain MOR. C1 neurons were identified by using an antibody against the epinephrine synthesizing enzyme phenylethanolamine-N-methyl transferase (PNMT), whereas MOR was localized by using an antipeptide antibody that recognizes the cloned MOR, MOR1. Combined immunoperoxidase and immunogold methods were used to examine the cellular distribution of MOR1 relative to PNMT-containing neurons in the RVL. MOR1 was found in 22{\%} of PNMT-containing dendrites (n = 392), whereas MOR1-containing axons or axon terminals contacted 14{\%} of PNMT-containing dendrites. This distribution was heterogenous with regard to dendritic size: PNMT-labeled dendrites containing MOR1 were usually large (60{\%} were >1.2 μm), whereas PNMT-containing dendrites that received MOR1-labeled afferents were usually small (79{\%} were <1.2 μm). Individual dendrites rarely contained MOR1 at both pre- and postsynaptic sites. Together these results suggest that MOR agonists may directly influence the activity of C1 neurons, as well as the activity of select afferents to these cells. Plasmalemmal membrane labeling for MOR1 was more frequent in smaller PNMT-containing dendrites, suggesting that postsynaptic receptors are more readily available for ligand binding in small dendrites, although the receptor was more frequently detected in larger PNMT dendrites. The selective distribution of MORs to specific pre- and postsynaptic sites suggests the receptor may be selectively trafficked to positions where it may regulate afferent activity that is heterogeneously distributed along the dendritic tree of C1 neurons.",
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