scholarly journals Localisation and activation of the neurokinin 1 receptor in the enteric nervous system of the mouse distal colon

2014 ◽  
Vol 356 (2) ◽  
pp. 319-332 ◽  
Author(s):  
Juan-Carlos Pelayo ◽  
Nicholas A. Veldhuis ◽  
Emily M. Eriksson ◽  
Nigel W. Bunnett ◽  
Daniel P. Poole
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Distal Colon ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

scholarly journals Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nick J. Spencer ◽  
Lee Travis ◽  
Lukasz Wiklendt ◽  
Marcello Costa ◽  
Timothy J. Hibberd ◽  
...  
Keyword(s):  
Nervous System ◽  
Smooth Muscle ◽  
Enteric Nervous System ◽  
Lymphatic Vessels ◽  
Distal Colon ◽  
Distal Region ◽  
Proximal Colon ◽  
Synchronous Firing ◽  
Electrophysiological Recordings ◽  
Intrinsic Neurons

AbstractHow the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion. Recordings showed pulsatile firing of excitatory and inhibitory neuromuscular inputs not only in proximal colon, but also distal colon, long before the propagating contraction invades the distal region. During propulsion, wavelet analysis revealed increased coherence at ~2 Hz over large distances between the proximal and distal regions. Therefore, during propulsion, synchronous firing of descending inhibitory nerve pathways over long ranges aborally acts to suppress smooth muscle from contracting, counteracting the excitatory nerve pathways over this same region of colon. This delays muscle contraction downstream, ahead of the advancing contraction. The mechanism identified is more complex than expected and vastly different from fluid propulsion along other hollow smooth muscle organs; like lymphatic vessels, portal vein, or ureters, that evolved without intrinsic neurons.

scholarly journals Establishment of an in vitro screening model of bioactive compounds from Vietnamese medicinal plants using the recombinant central nervous system receptors

2018 ◽  
Vol 34 (1) ◽  
Author(s):  
Pham Thi Hong Nhung ◽  
Dinh Doan Long
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Semliki Forest Virus ◽  
Viet Nam ◽  
In Vitro Screening ◽  
Binding Assays ◽  
Neurokinin 1 Receptor ◽  
Screening Model ◽  
Neurokinin 1

The central nervous system receptors are important targets of the drugs, involved in many neurological diseases. Therefore, this study was designed to build an in vitro screening model using recombinant receptors distributed in the central nervous system (CNS). Method: construction of cDNA system encoding for receptors; using Semliki Forest virus for the rapid and high expression of receptors in mammalian cell lines; designing binding assays for in vitro pharmacological studies of compounds and methanol plant extracts. Results: 24 cDNAs encoding for receptors and 1 screening kit with neurokinin-1 receptor were constructed; 4 receptors were expressed successfully. Conclusion: The in vitro screening model was established successfully and applied for NK1 receptors with high sensitivity and specificity. This model is a useful tool for discovery and development of target compounds acting in the CNS.   Keywords Recombinant CNS receptors, an in vitro screening assays, bioactive compounds, Semliki Forest virus. specificity References [1] Đỗ Huy Bích và cs, Cây thuốc và động vật làm thuốc ở Việt Nam, NXB Khoa học và kỹ thuật, 2004[2] Kenneth H. Lundstrom, M.L. Chiu, G Protein - Coupled receptors in Drug Discovery, Taylor & Francis Group, 2006[3] Zhu M., Bowery N.G., Greengrass P.M., Phillipson J.D., Application of radioligand receptor binding assays in the search for CNS active principles from Chinese medicinal plants, J. Ethnopharmacol. 54 (1996) 153[4] Phạm Thị Hồng Nhung, Hoàng Thị Mỹ Nhung, Đinh Đoàn Long, Cải biến vectơ hệ Virus Semliki Forest (SFV) nhằm biểu hiện thụ thể GPCR của người Việt Nam, Tạp chí Khoa học ĐHQGHN: Khoa học Tự nhiên và Công nghệ 31 (2015) 47[5] Berglund P., Sjoberg M., Garoff H., Atkins G.J., Sheahan B.J., and Liljestrom P., Semliki Forest virus expression system: production of conditionally infectious recombinant particles, Biotechnology 11 (1993) 916[6] Dinh DL, Pham THN, Hoang TMN, Trinh TC, Vo TTL, Pham TH, Kenneth L., Interaction of Vietnamese medicinal plant extracts with recombinantly expressed human neurokinin-1 receptor, Planta Medica Letters, 2(2015)42 [7] Rosso M., Mu᷈ Noz M., Berger M., The Role of Neurokinin -1 Receptor in the Microenvironment of Inflammation and Cancer, The Scientific World Journal, 2012 (2012)1[8] Tô Việt Bắc, Bùi Minh Đức, Phạm Thị Kim, Thử nghiệm khả năng gây độc trên chuột của chế phẩm rotundin, Tạp chí Y hoc Việt Nam, 7(1994)46[9] Violin J.D., Crombie A.L., Soergel D.G., Lark M.W., Biased ligands at G-protein-coupled receptors: promise and progress, Trends Pharmacol Sci, 35(2014) 308[10] Lundstrom K., Henningsen R., Semliki Forest virus vectors applied to receptor expression in cell lines and primary neurons, J. Neurochem 71 (1998) [11] Federal Register 58 No. 19, Addition of Appendix DL-X to the NIH guidelines regarding Semliki Forest virus. Human Gene Therapy. 1993. p.5.

Human and Mouse Enteric Nervous System Neurosphere Transplants Regulate the Function of Aganglionic Embryonic Distal Colon

2008 ◽  
Vol 135 (1) ◽  
pp. 205-216.e6 ◽  
Author(s):  
Richard M. Lindley ◽  
Daniel B. Hawcutt ◽  
M. Gwen Connell ◽  
Sarah N. Almond ◽  
Maria–Giuliana Vannucchi ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Distal Colon ◽  
Human And Mouse

scholarly journals Optogenetic activation of the distal colon epithelium engages enteric nervous system circuits to initiate motility patterns

2021 ◽  
Author(s):  
Sarah A Najjar ◽  
Brian Edwards ◽  
Kathryn M. Albers ◽  
Brian M Davis ◽  
Kristen M Smith-Edwards
Keyword(s):  
Nervous System ◽  
Epithelial Cells ◽  
Enteric Nervous System ◽  
Large Scale ◽  
Ex Vivo ◽  
Distal Colon ◽  
Proximal Colon ◽  
Nerve Fibers ◽  
Colon Motility ◽  
Neural Communication

Background & Aims: Digestive functions of the colon depend on sensory-motor reflexes in the enteric nervous system (ENS), initiated by intrinsic primary afferent neurons (IPANs). IPAN terminals project to the mucosal layer of the colon, allowing communication with epithelial cells comprising the colon lining. The chemical nature and functional significance of this epithelial-neural communication in regards to secretion and colon motility are of high interest. Colon epithelial cells can produce and release neuroactive substances such as ATP and 5-HT, which can activate receptors on adjacent nerve fibers, including IPAN subtypes. In this study we examined if stimulation of epithelial cells alone is sufficient to activate neural circuits that control colon motility. Methods: Optogenetics and calcium imaging were used in ex vivo preparations of the mouse colon to selectively stimulate the colon epithelium, measure changes in motility and record activity of neurons within the myenteric plexus. Results: Light-mediated activation of epithelial cells lining the distal, but not proximal, colon caused local contractions and increased the rate of colonic migrating motor complexes. Epithelial-evoked local contractions in the distal colon were reduced by both ATP and 5-HT receptor antagonists. Conclusions: Our findings indicate that colon epithelial cells likely utilize purinergic and serotonergic signaling to initiate activity in myenteric neurons, produce local contractions and facilitate large-scale coordination of ENS activity responsible for whole-colon motility patterns.

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