Complex actions of neurotensin in ascending and sigmoid colonic muscle: Involvement of enteric mediators

Azriel, Yael; Lu, Lingbin; Bucher, Elizabeth S.

doi:10.1016/j.ejphar.2010.06.049

Cited by 6 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regionally specific mechanisms were examined for NT-induced colonic contraction (Azriel et al, 2010). Whereas circular smooth muscle in the ascending and descending colon exhibited a direct contractile response to NT, the descending colon showed a greater influence from indirect mediators of NT signaling, such as tachykinins, prostaglandins, histamine, and nitric oxide.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neurotensin Modulates Pacemaker Activity in Interstitial Cells of Cajal from the Mouse Small Intestine

Lee

Park

Kim

et al. 2012

Molecules and Cells

View full text Add to dashboard Cite

Neurotensin, a tridecapeptide localized in the gut to discrete enteroendocrine cells of the small bowel mucosa, is a hormone that plays an important role in gastrointestinal secretion, growth, and motility. Neurotensin has inhibitory and excitatory effects on peristaltic activity and produces contractile and relaxant responses in intestinal smooth muscle. Our objective in this study is to investigate the effects of neurotensin in small intestinal interstitial cells of Cajal (ICC) and elucidate the mechanism. To determine the electrophysiological effects of neurotensin on ICC, whole-cell patch clamp recordings were performed in cultured ICC from the small intestine. Exposure to neurotensin depolarized the membrane of pacemaker cells and produced tonic inward pacemaker currents. Only neurotensin receptor1 was identified when RT-PCR and immunocytochemistry were performed with mRNA isolated from small intestinal ICC and c-Kit positive cells. Neurotensin-induced tonic inward pacemaker currents were blocked by external Na⁺-free solution and in the presence of flufenamic acid, an inhibitor of non-selective cation channels. Furthermore, neurotensin-induced action is blocked either by treatment with U73122, a phospholipase C inhibitor, or thapsigargin, a Ca²⁺-ATPase inhibitor in ICC. We found that neurotensin increased spontaneous intracellular Ca²⁺ oscillations as seen with fluo4/AM recording. These results suggest that neurotensin modulates pacemaker currents via the activation of non-selective cation channels by intracellular Ca²⁺-release through neurotensin receptor1.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Additionally, NT inhibits contractile activity in the guinea pig proximal colon and increases tonic contraction in the rat proximal colon (Kitabgi and Vincent, 1981;Mule et al, 1995). Furthermore, it was reported that different regionally specific mediators involve NT-induced action in GI smooth muscles (Azriel et al, 2010).…”

Section: Introductionmentioning

confidence: 98%

Neurotensin Modulates Pacemaker Activity in Interstitial Cells of Cajal from the Mouse Small Intestine

Lee

Park

Kim

et al. 2012

Molecules and Cells

View full text Add to dashboard Cite

show abstract

“…In the colon, neurotensin generally stimulates motility, though the specific effects may vary depending on the region, conditions, and species. Azriel et al [61 ] examined strips of human smooth muscle from the ascending and descending colon, and demonstrated regionally specific mechanisms for neurotensin-induced colonic contraction. Whereas circular smooth muscle in both areas exhibited a direct contractile response to neurotensin, the descending colon demonstrated a greater influence from 'indirect' mediators of neurotensin signaling such as tachykinins, prostaglandins, histamine, and nitric oxide.…”

Section: Neurotensin and Gastrointestinal Physiologymentioning

confidence: 98%

The role of neurotensin in physiologic and pathologic processes

Mustain

Rychahou

Evers

2011

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

115

View full text Add to dashboard Cite

The review highlights the wide array of biological processes in which neurotensin has a role, and summarizes the most recent advances in various fields of neurotensin research. The knowledge gained through this research has led to the development of first-in-class drugs for the treatment of various medical conditions, and it is clear that in the coming years some of these agents will be ready to move from the bench to the bedside in clinical trials.

show abstract

“…The production of NT Receptor 1 (NTSR1) and NTSR3 (but not NTSR2) was proven in sigmoid colon circular muscle and taenia coli. Functionally, this NP is responsible for direct (muscle) and indirect (neuronal/non-neuronal mechanism) smooth muscle contraction from ascending and sigmoid regions of the human colon, while the descending colon shows higher dependence on tachykinins (TAC), prostaglandins (PGEs), histamine and nitric oxide [57,58].…”

Section: Large Intestine Innervation As a Physiological Np Sourcementioning

confidence: 99%

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Kasprzak

Adamek

2020

IJMS

View full text Add to dashboard Cite

Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain–tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.

show abstract

Complex actions of neurotensin in ascending and sigmoid colonic muscle: Involvement of enteric mediators

Cited by 6 publications

References 37 publications

Neurotensin Modulates Pacemaker Activity in Interstitial Cells of Cajal from the Mouse Small Intestine

Neurotensin Modulates Pacemaker Activity in Interstitial Cells of Cajal from the Mouse Small Intestine

The role of neurotensin in physiologic and pathologic processes

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Contact Info

Product

Resources

About