ATP as a cotransmitter in sympathetic and parasympathetic nerves - another Burnstock legacy

Kennedy, Charles

doi:10.1016/j.autneu.2021.102860

Cited by 9 publications

(3 citation statements)

References 154 publications

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“…There is considerable evidence for excitatory co-transmission of ATP and acetycholine (ACh) from post-ganglionic parasympathetic nerve fibres to isolated detrusor muscle (Kennedy, 2015(Kennedy, , 2021. Contractions generated by trains of short (≤100 μs) pulses and labile to neuroactive agents such as tetrodotoxin or lignocaine are designated as nerve-mediated.…”

Section: Introductionmentioning

confidence: 99%

Frequency‐dependent characteristics of nerve‐mediated ATP and acetylcholine release from detrusor smooth muscle

Chakrabarty

Aitchison

White

et al. 2022

Experimental Physiology

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Nerve-mediated contractions of detrusor smooth muscle are mediated by acetylcholine (ACh) and ATP release in most animals. However, with the normal human bladder, only ACh is a functional transmitter, but in benign pathologies such as overactive bladder (OAB), ATP re-emerges as a secondary transmitter. The selective regulation of ATP release offers a therapeutic approach to manage OAB, in contrast to current primary strategies that target ACh actions. However, the release characteristics of nerve-mediated ACh and ATP are poorly defined and this study aimed to measure the frequency dependence of ACh and ATP release and determine if selective regulation of ATP or ACh was possible. Experiments were carried out in vitro with mouse detrusor with nerve-mediated ATP and ACh release measured simultaneously with tension recording. ATP was released in two frequency-dependent components, both at lower frequencies (mid-range 0.4 and 5.5 Hz stimulation) compared to a single compartment release of ACh at 14 Hz. Intervention with the phosphodiesterase type-5 inhibitor sildenafil attenuated ATP release, equally from both components, but had no effect on ACh release. These data demonstrate that nerve-mediated ACh and ATP release characteristics are distinct and may be separately manipulated. This offers a potential targeted drug model to manage benign lower urinary tract conditions such as OAB.

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Section: Introductionmentioning

confidence: 99%

Frequency‐dependent characteristics of nerve‐mediated ATP and acetylcholine release from detrusor smooth muscle

Chakrabarty

Aitchison

White

et al. 2022

Experimental Physiology

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“…Both pannexin hemichannels and P2X7 receptors are functionally associated and act together in many physiological processes (for examples see Saéz et al, 2017; Flores‐Muñoz et al, 2021; Maldifassi et al, 2021). Additionally, chromaffin cell P2X7 receptors might be also paracrinally activated by the ATP that is reportedly co‐released with acetylcholine from nerve endings (Kennedy, 2021).…”

Section: Discussionmentioning

confidence: 99%

Autocrine activation of P2X7 receptors mediates catecholamine secretion in chromaffin cells

Maldifassi,

Guerra‐Fernández,

Ponce

et al. 2024

British J Pharmacology

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Background and PurposeATP is highly accumulated in secretory vesicles and secreted upon exocytosis from neurons and endocrine cells. In adrenal chromaffin granules, intraluminal ATP reaches concentrations over 100 mM. However, how these large amounts of ATP contribute to exocytosis has not been investigated.Experimental ApproachExocytotic events in bovine and mouse adrenal chromaffin cells were measured with single cell amperometry. Cytosolic Ca2+ measurements were carried out in Fluo‐4 loaded cells. Submembrane Ca2+ was examined in PC12 cells transfected with a membrane‐tethered Ca2+ indicator Lck‐GCaMP3. ATP release was measured using the luciferin/luciferase assay. Knockdown of P2X7 receptors was induced with short interfering RNA (siRNA). Direct Ca2+ influx through this receptor was measured using a P2X7 receptor‐GCamp6 construct.Key ResultsATP induced exocytosis in chromaffin cells, whereas the ectonucleotidase apyrase reduced the release events induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP), high KCl, or ionomycin. The purinergic agonist BzATP also promoted a secretory response that was dependent on extracellular Ca2+. A740003, a P2X7 receptor antagonist, abolished secretory responses of these secretagogues. Exocytosis was also diminished in chromaffin cells when P2X7 receptors were silenced using siRNAs and in cells of P2X7 receptor knockout mice. In PC12 cells, DMPP induced ATP release, triggering Ca2+ influx through P2X7 receptors. Furthermore, BzATP, DMPP, and KCl allowed the formation of submembrane Ca2+ microdomains inhibited by A740003.Conclusion and ImplicationsAutocrine activation of P2X7 receptors constitutes a crucial feedback system that amplifies the secretion of catecholamines in chromaffin cells by favouring submembrane Ca2+ microdomains.

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“…Similar to muscle spindles, glutamate release from flower‐spray endings may regulate sensory excitability in an autocrine manner. On the other hand, previous studies reported the release of ATP from both sympathetic and parasympathetic nerves (review; Kennedy 2021). As VNUT, the vesicular protein responsible for the uptake of ATP, was observed in the varicosities of DBH‐immunoreactive sympathetic nerves in the present study, ATP may be released by exocytosis from sympathetic nerves to bind to P2 × 3 receptors in the flower‐spray endings closely associated with the sympathetic nerve.…”

Section: Discussionmentioning

confidence: 99%

Three‐Dimensional Ultrastructure of Flower‐Spray Nerve Endings in the Rat Carotid Sinus

Murakami,

Sasaki,

Komuro

et al. 2024

J of Comparative Neurology

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The flower‐spray nerve endings are afferent nerve terminals in the carotid sinus that arise from carotid sinus nerve of glossopharyngeal nerve. However, the three‐dimensional ultrastructural characteristics of flower‐spray nerve endings and spatial relationships between the terminal parts and other cellular elements have not been fully understood. To elucidate their detailed relationship, backscattered electron imaging of serial sections was performed with a scanning electron microscope to produce a three‐dimensional reconstruction of the flower‐spray endings. The terminal parts of flower‐spray endings were distributed horizontally approximately 5 µm outside the external elastic membrane in the tunica adventitia of the internal carotid artery. The three‐dimensional reconstruction showed that the terminal parts of flower‐spray endings were flat with irregular contours and were partially covered by the thin cytoplasmic processes of Schwann cells. The complex consisting of the nerve terminals and associated Schwann cells was surrounded by a multilayered basement membrane. The terminal parts of the endings were also surrounded by fibroblasts with elastic fibers and collagen fibrils. Secretory vesicles without an electron‐dense core were observed in the terminal parts of the endings. The accumulation of vesicles just below the axonal membrane was observed in terminal parts not covered by Schwann cell cytoplasmic processes on both the luminal and basal sides. Swollen mitochondria, concentric membranous structures, and glycogen granule‐like electron‐dense materials were often noted in some of the terminal parts of the endings and the parent axon. Collectively, the present results suggest that flower‐spray endings are baroreceptors because their morphology was similar to other mechanoreceptors. Furthermore, flower‐spray endings may be affected by glutamate secreted in an autocrine manner.

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ATP as a cotransmitter in sympathetic and parasympathetic nerves - another Burnstock legacy

Cited by 9 publications

References 154 publications

Frequency‐dependent characteristics of nerve‐mediated ATP and acetylcholine release from detrusor smooth muscle

Frequency‐dependent characteristics of nerve‐mediated ATP and acetylcholine release from detrusor smooth muscle

Autocrine activation of P2X7 receptors mediates catecholamine secretion in chromaffin cells

Three‐Dimensional Ultrastructure of Flower‐Spray Nerve Endings in the Rat Carotid Sinus

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