Neurotransmitters and peptides: Whispered secrets and public announcements
Open accessAbstract
The magnocellular oxytocin and vasopressin neurones of the hypothalamus are now understood in exceptional detail. Extensive quantitative details from many independent sources are available describing the electrical activity of the neurones in diverse circumstances, the subcellular localization of vesicles, and rates of hormone secretion from nerve endings into the blood and from dendrites into the brain. These data enable the relationship of electrical (spike) activity to vesicle exocytosis to be inferred with some precision. Such calculations lead to the conclusion that exocytosis of peptide-containing vesicles is a relatively rare event even in this vesicle-dense system. At any given release site in the neurohypophysis, it seems that several hundred spikes are needed on average to release a single vesicle. Release from compartments within the brain seems also to be very rare, making it implausible that peptides can act in a temporally precise, anatomically specific manner. However, very large amounts of peptide are released by these infrequent events, consistent with their likely role as neurohormonal messengers.
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Comparison of CSF neurophysin and oxytocin levels suggests that only about 5% of oxytocin released in the rat brain reaches the CSF.
“Comparing CSF levels of neurophysin and oxytocin suggests that only ~5% of the oxytocin that is released in the rat brain reaches the CSF (1).”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [1]
The paper’s Abstract compares CSF oxytocin with co-released neurophysin and estimates that about 80 oxytocin vesicles per second reach the CSF, versus about 4,000 released centrally. That implies roughly 2%, not the cited sentence’s ~5%. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredBehavioral effects require higher oxytocin concentrations than peripheral effects, because oxytocin receptors desensitize and peripheral receptors are exposed to much lower oxytocin levels and are therefore more sensitive.
“It is unsurprising that higher concentrations of oxytocin are needed for behavioral effects than for peripheral effects.As in most G protein-coupled receptors, agonist stimulation of oxytocin receptors leads to desensitization (27).Receptors at peripheral sites are exposed to much lower concentrations of oxytocin (1-10pg/ml), than receptors in the brain (1), so will be more sensitive to it.”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [1]
The indexed copy (section labeled Abstract; page unavailable) estimates oxytocin at approximately 1000 pg/ml in extracellular fluid of the supraoptic nucleus, supporting the cited point that brain concentrations can be high. It does not establish the stated peripheral concentration, greater peripheral receptor sensitivity, or the comparison of doses needed for behavioral and peripheral effects. The citing sentence attributes receptor desensitization to a different reference, (27). (LLM, conf=0.86)
Experimental — accuracy not yet measuredA more global form of OT and AVP release can occur when these neuropeptides are released from non-synaptic regions of neurons, such as dendrites.
“A more global form of OT and AVP release can occur when these neuropeptides are released from non-synaptic regions of neurons (e.g., dendrites) (Figure 6) [108; 109; 110].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [108]
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- Authors
- Leng, G., & Ludwig, M.
- Affiliations
- University of Edinburgh (GB)
- Corresponding author
- Leng, Gareth
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2008-11-28
- Volume
- 586
- Issue
- 23
- Pages
- 5625-5632
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2655398
- OpenAlex
- W1580839038
- Cited by
- 168
- References
- 58
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 8 · 2021: 11 · 2020: 4 · 2019: 6 · 2018: 15 · 2017: 11 · 2016: 13 · 2015: 11 · 2014: 10 · 2013: 13 · 2012: 11
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council (BB/E015123/1)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- oxytocin, vasopressin, magnocellular neurons, hypothalamus, neurohypophysis, vesicle exocytosis, action potential firing rate, peptide release, neurohormones
- MeSH terms
- Action Potentials, Animals, Exocytosis, Humans, Hypothalamus, Neuropeptides, Oxytocin, Vasopressins, Neurotransmitter Agents, Transport Vesicles
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