Comprehensive Physiology Wiley Online Library

Cellular Aspects of Catecholaminergic Neurons

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Abstract

The sections in this article are:

1 Terminology
2 Historical Developments
2.1 Identification of the Sympathetic Transmitter
2.2 Tissue Receptors
2.3 Autonomic Neuroeffector Junctions
2.4 Biochemical Mechanisms
3 Distribution and Storage of Catecholamines
3.1 Tissue Distribution
3.2 Cellular Distribution of Catecholamines
3.3 Subcellular Distribution
3.4 Quantitative Aspects of Transmitter Distribution
3.5 Summary
4 Enzymes Involved in Catecholamine Metabolism
4.1 Biosynthetic Ezymes
4.2 Degradative Enzymes
4.3 Regulation of Catecholamine Turnover
4.4 Summary
5 Release and Inactivation of Catecholamines
5.1 Quantal Liberation of Transmitter by Exocytosis
5.2 Inactivation of Transmitter
5.3 Circulating Catecholamines and Dopamine β‐hydroxy lase
6 Adrenotropic Receptors
6.1 Classification of Adrenotropic Receptors
6.2 Receptor Topography
6.3 Receptor Composition
7 Life Cycle of Noradrenergic Synaptic Vesicles
7.1 Origin of Vesicles Within Noradrenergic Neurons
7.2 Turnover and Fate of Synaptic Vesicles
7.3 Topochemical Model of Noradrenergic Transmission
Figure 1. Figure 1.

Noradrenaline assays. Phenylethanolamine N‐methyltransferase (PNMT), S‐adenosylmethionine (SAM), 14C (*).

Figure 2. Figure 2.

Fluorescence histochemistry of sympathetic neurons, × 6,000. Top: cell bodies and processes in section of rat lumbar ganglion. Bottom: whole stretch mount of rat iris showing varicose nerve terminals innervating smooth muscle of iris and blood vessel.

Courtesy T. B. Cheah, unpublished observations
Figure 3. Figure 3.

Horizontal representation of ascending noradrenergic and dopaminergic pathways in the rat brain. Not shown are adrenergic pathways that arise from the rostral portions of A1 and A2 .

From Livett modified from Ungerstedt
Figure 4. Figure 4.

Electron micrographs of sympathetic axon terminals innervating smooth muscle, × 66,000. Top: section of cat spleen fixed in osmic acid. Bottom: freeze‐etch replica of mouse vas deferens. Smooth muscle (SM) Schwann cell (SCH), axon (A), large vesicle (LV), small vesicle (SV), collagen (COL)

Courtesy A. Ostberg and D. Devine
Figure 5. Figure 5.

Pathway of catecholamine synthesis showing enzymes and cofactors involved: tyrosine hydroxylase (TH), dihydropteridine reductase (DPR), L‐aromatic amino acid decarboxylase (AADC), dopamine β‐hydroxylase (DBH), phenylethanolamine N‐methyltransferase (PNMT), S‐adenosylmethionine (S‐Am), S‐adenosylhomocysteine (S‐Ah).

Figure 6. Figure 6.

Immunohistochemical localization of transmitter‐synthesizing enzymes in brainstem neurons. Top: immunoperoxidase localization of tyrosine hydroxylase.

Courtesy V. Pickel, unpublished observations. Bottom: immunofluorescent localization of dopamine β‐hydroxylase. Courtesy B. Hartmann, unpublished observations
Figure 7. Figure 7.

Pathway of noradrenaline (NA) catabolism showing the enzymes involved: catechol‐O‐methyltransferase (COMT), monoamine oxidase (MAO), aldehyde dehydrogenase (ADH), aldehyde reductase (AR), normetadrenaline (NM), 3‐methoxy‐4‐hydroxymandelic acid (VMA), 3‐methoxy‐4‐hydroxyphenylethylglycol (MOPEG).

Figure 8. Figure 8.

Electron micrograph of sympathetic nerve terminals in rat vas deferens showing fusion of membranes of synaptic vesicles (cored at ↑ and empty at ↦) with axonal membrane. × 160,000.

From Fillenz
Figure 9. Figure 9.

Hypothetical life cycle of noradrenergic synaptic vesicles. Vesicle proteins (+) are synthesized by ribosomes in the endoplasmic reticulum (rer) of the cell body and assembled into large granular vesicles (lgv) in the Golgi endoplasmic reticulum (ger). These vesicles can synthesize and store noradrenaline (•) and are exported into the axon terminals by an axoplasmic transport system involving neurotubules (nt). The large granular vesicles are transformed into small granular vesicles in the axon varicosities in one of three hypothetical ways: A, large granular vesicles are gradually transformed into small granular vesicles as a result of repetitive exocytosis with progressive loss of vesicle constituents, including membrane proteins such as DBH; B, large granular vesicles undergo a single exocytosis, releasing soluble proteins from their cores only and forming multiple small granular vesicles from their retrieved membranes; C, small granular vesicles are formed locally from large granular vesicles by budding, or some other form of transfer of contents, and are the only vesicles involved in exocytosis.

From Geffen & Rush
Figure 10. Figure 10.

Topochemical model of noradrenergic transmission showing pathways involved in the synthesis, storage, release, reception, and inactivation of noradrenaline. Chromogranin (CG), normetadrenaline (NM), noradrenaline (NA). See text for remaining abbreviations.



Figure 1.

Noradrenaline assays. Phenylethanolamine N‐methyltransferase (PNMT), S‐adenosylmethionine (SAM), 14C (*).



Figure 2.

Fluorescence histochemistry of sympathetic neurons, × 6,000. Top: cell bodies and processes in section of rat lumbar ganglion. Bottom: whole stretch mount of rat iris showing varicose nerve terminals innervating smooth muscle of iris and blood vessel.

Courtesy T. B. Cheah, unpublished observations


Figure 3.

Horizontal representation of ascending noradrenergic and dopaminergic pathways in the rat brain. Not shown are adrenergic pathways that arise from the rostral portions of A1 and A2 .

From Livett modified from Ungerstedt


Figure 4.

Electron micrographs of sympathetic axon terminals innervating smooth muscle, × 66,000. Top: section of cat spleen fixed in osmic acid. Bottom: freeze‐etch replica of mouse vas deferens. Smooth muscle (SM) Schwann cell (SCH), axon (A), large vesicle (LV), small vesicle (SV), collagen (COL)

Courtesy A. Ostberg and D. Devine


Figure 5.

Pathway of catecholamine synthesis showing enzymes and cofactors involved: tyrosine hydroxylase (TH), dihydropteridine reductase (DPR), L‐aromatic amino acid decarboxylase (AADC), dopamine β‐hydroxylase (DBH), phenylethanolamine N‐methyltransferase (PNMT), S‐adenosylmethionine (S‐Am), S‐adenosylhomocysteine (S‐Ah).



Figure 6.

Immunohistochemical localization of transmitter‐synthesizing enzymes in brainstem neurons. Top: immunoperoxidase localization of tyrosine hydroxylase.

Courtesy V. Pickel, unpublished observations. Bottom: immunofluorescent localization of dopamine β‐hydroxylase. Courtesy B. Hartmann, unpublished observations


Figure 7.

Pathway of noradrenaline (NA) catabolism showing the enzymes involved: catechol‐O‐methyltransferase (COMT), monoamine oxidase (MAO), aldehyde dehydrogenase (ADH), aldehyde reductase (AR), normetadrenaline (NM), 3‐methoxy‐4‐hydroxymandelic acid (VMA), 3‐methoxy‐4‐hydroxyphenylethylglycol (MOPEG).



Figure 8.

Electron micrograph of sympathetic nerve terminals in rat vas deferens showing fusion of membranes of synaptic vesicles (cored at ↑ and empty at ↦) with axonal membrane. × 160,000.

From Fillenz


Figure 9.

Hypothetical life cycle of noradrenergic synaptic vesicles. Vesicle proteins (+) are synthesized by ribosomes in the endoplasmic reticulum (rer) of the cell body and assembled into large granular vesicles (lgv) in the Golgi endoplasmic reticulum (ger). These vesicles can synthesize and store noradrenaline (•) and are exported into the axon terminals by an axoplasmic transport system involving neurotubules (nt). The large granular vesicles are transformed into small granular vesicles in the axon varicosities in one of three hypothetical ways: A, large granular vesicles are gradually transformed into small granular vesicles as a result of repetitive exocytosis with progressive loss of vesicle constituents, including membrane proteins such as DBH; B, large granular vesicles undergo a single exocytosis, releasing soluble proteins from their cores only and forming multiple small granular vesicles from their retrieved membranes; C, small granular vesicles are formed locally from large granular vesicles by budding, or some other form of transfer of contents, and are the only vesicles involved in exocytosis.

From Geffen & Rush


Figure 10.

Topochemical model of noradrenergic transmission showing pathways involved in the synthesis, storage, release, reception, and inactivation of noradrenaline. Chromogranin (CG), normetadrenaline (NM), noradrenaline (NA). See text for remaining abbreviations.

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L. B. Geffen, B. Jarrott. Cellular Aspects of Catecholaminergic Neurons. Compr Physiol 2011, Supplement 1: Handbook of Physiology, The Nervous System, Cellular Biology of Neurons: 521-571. First published in print 1977. doi: 10.1002/cphy.cp010115