Role of cyclooxygenases 1 and 2 in the modulation of neuromuscular functions in the distal colon of humans and mice

Fornai, Matteo; Blandizzi, Corrado; Colucci, Rocchina; Antonioli, Luca; Bernardini, Nunzia; Segnani, Cristina; Baragatti, Barbara; Barogi, Silvia; Berti, Piero; Spisni, Roberto; Tacca, M. Del

doi:10.1136/gut.2004.053322

Cited by 53 publications

(70 citation statements)

References 37 publications

(30 reference statements)

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“…Stimulation with 0.1 μM nicotine had no effect and 0.3 μM nicotine had only a limited effect on the preparations from each region (data not shown). A role for cyclooxygenases is proposed in the modulation of neuromuscular functions in the mouse and human distal colon (24). However, treatment of the distal colon with 10 and 20 μM indomethacin for 30 min did not change the relaxation induced by nicotine; the responses induced by 1 and 3 μM nicotine in the indomethacin-treated preparations were 21% (peak relaxation) and 28%, respectively, which were almost the same as those in the control in a typical experiment (n = 2).…”

Section: Nicotine-induced Relaxation In Longitudinal Preparations Fromentioning

confidence: 99%

Nicotine-Induced Neurogenic Relaxation in the Mouse Colon: Changes With Dextran Sodium Sulfate–Induced Colitis

et al. 2009

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Abstract. Nicotine has been shown to reduce both tone and muscular activity in the human colon by releasing nitric oxide (NO) from nerves. To our knowledge, however, the effect of nicotine on mouse colon has not been elucidated, and the response in tissue from ulcerative colitis (UC) has not been investigated. We examined nicotine-induced responses in colon from control mice and mice with dextran sodium sulfate (DSS)-induced UC. In controls, bath application of nicotine caused a transient relaxation in longitudinal preparations from the transverse and distal colons but not from the rectum. The response was observed in the presence of bethanechol, abolished by treatment with tetrodotoxin and hexamethonium, and mediated partially (>50%) by the NO pathway. In longitudinal preparations of the distal colon from DSStreated mice, spontaneous contractions decreased markedly, and nicotine caused contraction without relaxation in half of the preparations tested. Nicotine-induced relaxation in the presence of bethanechol was significantly decreased in the DSS-treated distal colon without changing bethanechol-induced contractions. These data suggest that 1) responses to nicotine differ dependent on colon regions, 2) DSS treatment predominantly caused nicotine-sensitive neurogenic changes in distal colon, and 3) DSS treatment may reverse the direction of nicotine-evoked responses in the colon, in mice.

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Section: Nicotine-induced Relaxation In Longitudinal Preparations Fromentioning

confidence: 99%

Nicotine-Induced Neurogenic Relaxation in the Mouse Colon: Changes With Dextran Sodium Sulfate–Induced Colitis

et al. 2009

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“…21 Specimens of mesenteric vessels were disrupted with cold glass pestles, and total RNA was isolated by TRIzol (Life Technologies) and chloroform. Total RNA (1 g) served as a template for cDNA synthesis in a reaction based on moloney murine leukemia virus reverse transcriptase.…”

Section: Rna Extraction and Rt-pcrmentioning

confidence: 99%

Cyclooxygenase-1 Is Involved in Endothelial Dysfunction of Mesenteric Small Arteries From Angiotensin II–Infused Mice

et al. 2007

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Abstract-Angiotensin II induces endothelial dysfunction by reducing NO availability and increasing reactive oxygen species. We assessed whether cyclooxygenase (COX)-1 or COX-2 participate in the angiotensin II-induced endothelial dysfunction in murine mesenteric small arteries and examined the role of reduced nicotinamide-adenine dinucleotide phosphate-dependent reactive oxygen species production. Mice received angiotensin II (600 ng/kg per minute, SC), saline (controls), angiotensin II ϩ apocynin (reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, 2.5 mg/day), or apocynin alone for 2 weeks. Endothelial function of mesenteric arteries was assessed by pressurized myograph. In controls, acetylcholine-induced relaxation was inhibited by N G -monomethyl-L-arginine and unaffected by DFU (COX-2 inhibitor), SC-560 (COX-1 inhibitor), or ascorbic acid. In angiotensin II-infused animals, the attenuated response to acetylcholine was less sensitive to N G -monomethyl-L-arginine, unaffected by DFU, and enhanced by SC-560 and, similarly, by SQ-29548, a thromboxane-prostanoid receptor antagonist. Moreover, response to acetylcholine was unchanged by ozagrel, a thromboxane synthase inhibitor, and normalized by ascorbic acid. Apocynin prevented the angiotensin II-induced vascular dysfunctions. In angiotensin II-infused mice, RT-PCR analysis showed a significant COX-2 downregulation, whereas COX-1 expression was upregulated. These changes were unaffected by apocynin. Modulation of COX isoform by angiotensin II was also documented by immunohistochemistry. In small mesenteric vessels, the reduced NO availability and oxidant excess, which characterize endothelial dysfunction secondary to angiotensin II, are associated with a reduced COX-2 and an increased COX-1 function and expression. Angiotensin II causes an oxidative stress-independent COX-1 overexpression, whereas angiotensin II-mediated oxidant excess production stimulates COX-1 activity to produce a contracting prostanoid endowed with agonist activity on thromboxane-prostanoid receptors. Key Words: angiotensin II Ⅲ microcirculation, cyclooxygenase Ⅲ endothelium Ⅲ oxidative stress I t is widely accepted that angiotensin (Ang) II is greatly implicated in the development of endothelial dysfunction in small resistance arteries, 1,2 mainly through an increased generation of reactive oxygen species (ROS) via vascular reduced nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activation. [3][4][5][6] Mesenteric arteries from Ang II-infused mice are characterized by a blunted endothelium-dependent relaxation, as a consequence of a reduced NO availability because of oxidant excess. 5 Recent evidence indicates that another pathway involved in endothelial dysfunction is cyclooxygenase (COX) activity. Thus, prostaglandins (PGs) have been shown to play a major role in modulating vascular tone, and COX represents a key enzyme in PG synthesis. Indeed, COX metabolizes arachidonic acid into the unstable intermediate PGH 2 , which, in turn, is converted by an array...

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“…As a result, there is no effective medical treatment for obstruction other than surgical resection or decompression (44,46). Nevertheless, even if obstruction is surgically removed or corrected, many patients experience a prolonged disturbance of motility function in the bowel proximal to resection (10,14,16). Therefore, there is a great need of effective medical treatments to relieve symptoms related to motility dysfunction in obstruction.…”

mentioning

confidence: 99%

“…Cyclooxygenase (COX) is an enzyme that catalyzes the major rate-limiting step of the synthesis of prostaglandins (PGs), which play important roles in mediating smooth muscle contractility in the gastrointestinal (GI) tract (10,19,23,27,33,38,49). Whereas COX-1 is the constitutive isoform of COX in most cell types, COX-2 is the inducible form within certain cells such as smooth muscle cells (SMC).…”

mentioning

confidence: 99%

Prophylactic and therapeutic benefits of COX-2 inhibitor on motility dysfunction in bowel obstruction: roles of PGE₂ and EP receptors

Lin

Sarna

Shi

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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We reported previously that mechanical stretch in rat colonic obstruction induces cyclooxygenase (COX)-2 expression in smooth muscle cells. The aims of the present study were to investigate whether in vivo treatment with COX-2 inhibitor has prophylactic and therapeutic effects on motility dysfunction in colon obstruction, and if so what are the underlying mechanisms. Partial colon obstruction was induced with a silicon band in the distal colon of 6 -8-wk-old Sprague-Dawley rats; obstruction was maintained for 3 days or 7 days. Daily administration of COX-2 inhibitor NS-398 (5 mg/kg) or vehicle was started before or after the induction of obstruction to study its prophylactic and therapeutic effects, respectively. The smooth muscle contractility was significantly suppressed, and colonic transit rate was slower in colonic obstruction. Prophylactic treatment with NS-398 significantly prevented the impairments of colonic transit and smooth muscle contractility and attenuated fecal collection in the occluded colons. When NS-398 was administered therapeutically 3 days after the initiation of obstruction, the muscle contractility and colonic transit still improved on day 7. Obstruction led to marked increase of COX-2 expression and prostaglandin E 2 (PGE2) synthesis. Exogenous PGE2 decreased colonic smooth muscle contractility. All four PGE2 E-prostanoid receptor types (EP1 to EP4) were detected in rat colonic muscularis externa. Treatments with EP1 and EP3 antagonists suppressed muscle contractility in control tissue but did not improve contractility in obstruction tissue. On the contrary, the EP2 and EP4 antagonists did not affect control tissue but significantly restored muscle contractility in obstruction. We concluded that our study shows that COX-2 inhibitor has prophylactic and therapeutic benefits for motility dysfunction in bowel obstruction. PGE2 and its receptors EP2 and EP4 are involved in the motility dysfunction in obstruction, whereas EP1 and EP3 mediate PGE2 regulation of colonic smooth muscle contractile function in normal state.

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Role of cyclooxygenases 1 and 2 in the modulation of neuromuscular functions in the distal colon of humans and mice

Cited by 53 publications

References 37 publications

Nicotine-Induced Neurogenic Relaxation in the Mouse Colon: Changes With Dextran Sodium Sulfate–Induced Colitis

Nicotine-Induced Neurogenic Relaxation in the Mouse Colon: Changes With Dextran Sodium Sulfate–Induced Colitis

Cyclooxygenase-1 Is Involved in Endothelial Dysfunction of Mesenteric Small Arteries From Angiotensin II–Infused Mice

Prophylactic and therapeutic benefits of COX-2 inhibitor on motility dysfunction in bowel obstruction: roles of PGE₂ and EP receptors

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Role of cyclooxygenases 1 and 2 in the modulation of neuromuscular functions in the distal colon of humans and mice

Cited by 53 publications

References 37 publications

Nicotine-Induced Neurogenic Relaxation in the Mouse Colon: Changes With Dextran Sodium Sulfate–Induced Colitis

Nicotine-Induced Neurogenic Relaxation in the Mouse Colon: Changes With Dextran Sodium Sulfate–Induced Colitis

Cyclooxygenase-1 Is Involved in Endothelial Dysfunction of Mesenteric Small Arteries From Angiotensin II–Infused Mice

Prophylactic and therapeutic benefits of COX-2 inhibitor on motility dysfunction in bowel obstruction: roles of PGE2 and EP receptors

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Prophylactic and therapeutic benefits of COX-2 inhibitor on motility dysfunction in bowel obstruction: roles of PGE₂ and EP receptors