Comprehensive Physiology Wiley Online Library

Biochemistry and Physiology of Serotonergic Transmission

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Serotonin Biosynthesis
1.1 Introductory Overview
1.2 Decarboxylation
1.3 Hydroxylation
2 Regulation of Serotonin Biosynthesis
2.1 Introductory Overview
2.2 Availability of Precursor Tryptophan
2.3 Feedback Control of Serotonin Biosynthesis
2.4 Inhibition of Tryptophan Hydroxylase: Serotonin Depletion
2.5 Chlorinated Amphetamines
3 Serotonin Metabolism
3.1 Introductory Overview
3.2 Oxidative Deamination
3.3 Conjugation
3.4 O‐Sulfation
3.5 N‐ and O‐Methylation
3.6 Inactivation of Circulating Serotonin
3.7 Pineal Gland
4 Uptake of Serotonin
4.1 Introductory Overview
4.2 Specific Uptake
4.3 Inhibition of Serotonin Uptake
5 Localization of Serotonin
5.1 Methodological Considerations
5.2 Identification of Monoamines
5.3 Serotonin Neurons
5.4 Regeneration of Serotonin Neurons
6 Molluscs
7 Serotonin Receptors, Antagonists, and Synaptic Effects
7.1 Myenteric Plexus
7.2 Ponto‐Geniculo‐Occipital Waves
7.3 Serotonin Receptor Isolation
8 Conclusion
Figure 1. Figure 1.

Articles on serotonin since 1951 plotted by years. The synthetic compound became available for scientific use in 1951. p‐Chlorophenylalanine, an effective tryptophan hydroxylase inhibitor, was introduced in 1966.

Figure 2. Figure 2.

Biosynthesis of serotonin from tryptophan.

Figure 3. Figure 3.

The activities of brain 5‐hydroxytryptophan (5‐HTP) and dopa decarboxylases (D) as a function of pH. Assay conditions for dopa decarboxylase (135 μg brain): 0.7 mM pyridoxal phosphate, 5.0 mM L‐dopa, 5.0 mM ascorbate, 75 mM imidazole or Tris buffer; incubation for 30 min at 38°C. Assay conditions for 5‐HTP decarboxylase (200 μg of brain): 0.7 mM pyridoxal phosphate, 1.0 mM L‐5‐HTP, 75 mM imidazole, Tris, or AMP; incubation for 90 min at 38°C. All plotted points represent the final pH of the completed mixture prior to incubation.

From Sims et al.
Figure 4. Figure 4.

The position of the raphe nuclei is shown on a sagittal view of the cat's brain. Horsley‐Clarke stereotaxic coordinates are shown on the scale below the drawing. C.s., nucleus centralis superior; D.b.c., decussation of the brachium conjunctivum; I.p., nucleus interpeduncularis; L.i., nucleus linearis intermedius; L.r., nucleus linearis rostralis; P., pyramid; R.d., nucleus raphe dorsalis; R.m., nucleus raphe magnus; R.o., nucleus raphe obscurus; R.p., nucleus raphe pontis; R.pa., nucleus raphe pallidus; T., trapezoid body

Adapted from Simon et al.
Figure 5. Figure 5.

Schematic diagram of serotonin neurons and pathways. The stippled regions show the location of groups of cell bodies in the lower brainstem. The correspondence between the indicated code of Dahlström & Fuxe and some named nuclear groups is as follows : B1, raphe pallidus; B2, raphe obscurus; B3, raphe magnus; B7, raphe dorsalis; B8, raphe medianus; B9, raphe mesencephalic. Ascending and descending projections are indicated.

From Fuxe & Jonsson , copyright 1974 by Raven Press, New York
Figure 6. Figure 6.

Biosynthesis of melatonin from serotonin: a pineal pathway.

Figure 7. Figure 7.

A schematic diagram of the ascending monoamine bundles in the lateral hypothalamic area. C, crus cerebri; F, fornix; FMT, fasciculus mammillothalamicus; LM, medial lemniscus; FR, fasciculus retroflexus (tractus habenulointerpeduncularus); NA, norepinephrine (noradrenaline); DA, dopamine; 5‐HT, 5‐hydroxytryptamine.

From Fuxe & Jonsson , copyright 1974 by Raven Press, New York


Figure 1.

Articles on serotonin since 1951 plotted by years. The synthetic compound became available for scientific use in 1951. p‐Chlorophenylalanine, an effective tryptophan hydroxylase inhibitor, was introduced in 1966.



Figure 2.

Biosynthesis of serotonin from tryptophan.



Figure 3.

The activities of brain 5‐hydroxytryptophan (5‐HTP) and dopa decarboxylases (D) as a function of pH. Assay conditions for dopa decarboxylase (135 μg brain): 0.7 mM pyridoxal phosphate, 5.0 mM L‐dopa, 5.0 mM ascorbate, 75 mM imidazole or Tris buffer; incubation for 30 min at 38°C. Assay conditions for 5‐HTP decarboxylase (200 μg of brain): 0.7 mM pyridoxal phosphate, 1.0 mM L‐5‐HTP, 75 mM imidazole, Tris, or AMP; incubation for 90 min at 38°C. All plotted points represent the final pH of the completed mixture prior to incubation.

From Sims et al.


Figure 4.

The position of the raphe nuclei is shown on a sagittal view of the cat's brain. Horsley‐Clarke stereotaxic coordinates are shown on the scale below the drawing. C.s., nucleus centralis superior; D.b.c., decussation of the brachium conjunctivum; I.p., nucleus interpeduncularis; L.i., nucleus linearis intermedius; L.r., nucleus linearis rostralis; P., pyramid; R.d., nucleus raphe dorsalis; R.m., nucleus raphe magnus; R.o., nucleus raphe obscurus; R.p., nucleus raphe pontis; R.pa., nucleus raphe pallidus; T., trapezoid body

Adapted from Simon et al.


Figure 5.

Schematic diagram of serotonin neurons and pathways. The stippled regions show the location of groups of cell bodies in the lower brainstem. The correspondence between the indicated code of Dahlström & Fuxe and some named nuclear groups is as follows : B1, raphe pallidus; B2, raphe obscurus; B3, raphe magnus; B7, raphe dorsalis; B8, raphe medianus; B9, raphe mesencephalic. Ascending and descending projections are indicated.

From Fuxe & Jonsson , copyright 1974 by Raven Press, New York


Figure 6.

Biosynthesis of melatonin from serotonin: a pineal pathway.



Figure 7.

A schematic diagram of the ascending monoamine bundles in the lateral hypothalamic area. C, crus cerebri; F, fornix; FMT, fasciculus mammillothalamicus; LM, medial lemniscus; FR, fasciculus retroflexus (tractus habenulointerpeduncularus); NA, norepinephrine (noradrenaline); DA, dopamine; 5‐HT, 5‐hydroxytryptamine.

From Fuxe & Jonsson , copyright 1974 by Raven Press, New York
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Michael D. Gershon. Biochemistry and Physiology of Serotonergic Transmission. Compr Physiol 2011, Supplement 1: Handbook of Physiology, The Nervous System, Cellular Biology of Neurons: 573-623. First published in print 1977. doi: 10.1002/cphy.cp010116