Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine

2001 ◽  
Vol 305 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Salmhofer H. ◽  
Neuhuber W. ◽  
Ruth P. ◽  
Huber A. ◽  
Russwurm M. ◽  
...  
2017 ◽  
Vol 313 (5) ◽  
pp. G419-G433 ◽  
Author(s):  
Leonie Durnin ◽  
Andrea Lees ◽  
Sheerien Manzoor ◽  
Kent C. Sasse ◽  
Kenton M. Sanders ◽  
...  

Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα+) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in KitW/KitW-v ( W/Wv) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD+)/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5′-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/Wv, Nos1−/−, and Prkg1−/− mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/Wv mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/Wv mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric oxide (NO) and intramuscular interstitial cells of Cajal (ICC-IM) in modulating neural release of purines in colon. We found that NO inhibited release of purines in human, monkey, and murine colons and that colons from KitW/KitW-v ( W/Wv) mice, which present with partial loss of ICC-IM, demonstrated augmented neural release of purines. Interactions between nitrergic and purinergic neurotransmission may affect motility in disease conditions with ICC-IM deficiencies.


2014 ◽  
Vol 307 (1) ◽  
pp. G98-G106 ◽  
Author(s):  
Barbara Lies ◽  
Víctor Gil ◽  
Dieter Groneberg ◽  
Barbara Seidler ◽  
Dieter Saur ◽  
...  

Nitric oxide (NO) is a major inhibitory neurotransmitter in the gastrointestinal (GI) tract. Its main effector, NO-sensitive guanylyl cyclase (NO-GC), is expressed in several GI cell types, including smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and fibroblast-like cells. Up to date, the interplay between neurons and these cells to initiate a nitrergic inhibitory junction potential (IJP) is unclear. Here, we investigate the origin of the nitrergic IJP in murine fundus and colon. IJPs were determined in fundus and colon SMC of mice lacking NO-GC globally (GCKO) and specifically in SMC (SM-GCKO), ICC (ICC-GCKO), and both SMC/ICC (SM/ICC-GCKO). Nitrergic IJP was abolished in ICC-GCKO fundus and reduced in SM-GCKO fundus. In the colon, the amplitude of nitrergic IJP was reduced in ICC-GCKO, whereas nitrergic IJP in SM-GCKO was reduced in duration. These results were corroborated by loss of the nitrergic IJP in global GCKO. In conclusion, our results prove the obligatory role of NO-GC in ICC for the initiation of an IJP. NO-GC in SMC appears to enhance the nitrergic IJP, resulting in a stronger and prolonged hyperpolarization in fundus and colon SMC, respectively. Thus NO-GC in both cell types is mandatory to induce a full nitrergic IJP. Our data from the colon clearly reveal the nitrergic IJP to be biphasic, resulting from individual inputs of ICC and SMC.


2011 ◽  
Vol 47 (2) ◽  
pp. 72 ◽  
Author(s):  
Pyung Jin Yoon ◽  
Shanker Prasad Parajuli ◽  
Dong Chuan Zuo ◽  
Pawan Kumar Shahi ◽  
Hyung Jung Oh ◽  
...  

2004 ◽  
Vol 95 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Tadayoshi Takeuchi ◽  
Kaori Fujinami ◽  
Akikazu Fujita ◽  
Yutaka Okishio ◽  
Tadashi Takewaki ◽  
...  

2016 ◽  
Vol 390 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Mohamed Abd-Elbaset ◽  
El-Shaimaa A. Arafa ◽  
Gamal A. El Sherbiny ◽  
Mohamed S. Abdel-Bakky ◽  
Abdel Nasser A.M. Elgendy

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