Caveolin-1 knockout alters β-adrenoceptors function in mouse small intestine

2006 ◽  
Vol 291 (6) ◽  
pp. G1020-G1030 ◽  
Author(s):  
Ahmed F. El-Yazbi ◽  
Woo Jung Cho ◽  
Richard Schulz ◽  
Edwin E. Daniel

β-Adrenoceptors are G protein-coupled receptors whose functions are closely associated with caveolae in the heart and cultured cell lines. In the gut, they are responsible, at least in part, for the mediation of the sympathetic stimulation that might lead to intestinal paralysis postoperatively. We examined the effect of caveolin-1 knockout on the β-adrenoceptor response in mouse small intestine. The relaxation response to (−)-isoprenaline in carbachol-contracted small intestinal tissue segments was reduced in caveolin-1 knockout mice (cav1−/−) compared with their genetic controls (cav1+/+). Immunohistochemical staining showed that β-adrenoceptor expression was similar in both strains in gut smooth muscle. Selective β-adrenoceptor blockers shifted the concentration response curve (CRC) of (−)-isoprenaline to the right in cav1+/+ intestine, but not in cav1−/−, with greatest shift in case of the β3-blocker, SR59230A. The CRC of the selective β3-agonist BRL 37344 was also shifted to the right in cav1−/− compared with cav1+/+. The cAMP-dependent protein kinase (PKA) inhibitor H-89 shifted the CRC of (−)-isoprenaline to the right in cav1+/+ but not in cav1−/−. H-89 reduced the relaxation due to forskolin and dibutyryl cAMP in cav1+/+ but not in cav1−/−, suggesting a reduction in PKA activity in cav1−/−. In cav1+/+, PKA was colocalized with caveolin-1 in the cell membrane, but PKA immunoreactivity persisted in cav1−/−. Examination of PKA expression in the lipid raft-rich membrane fraction of the jejunum revealed reduced PKA expression in cav1−/− compared with cav1+/+. The results of the present study show that the function of β-adrenoceptors is reduced in cav1−/− small intestine likely owing to reduced PKA activity.

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Natasha Jane Williams ◽  
Robin van den Boom

A 12-year-old Arabian gelding presented to the University of Adelaide for investigation of a firm subcutaneous mass, just proximal to the digital flexor tendon sheath of the right forelimb, that had appeared two weeks prior. The skin overlying the mass was intact. Fine needle aspiration identified eosinophilic and mastocytic infiltrates. One week later, the gelding re-presented for persistent colic signs. Blood examination showed eosinophilia, and on palpation per rectum the mesenteric root was very firm and enlarged and a number of small intestinal loops had subjectively thickened walls. Colic signs were unabated by the administration of pain relief. The owner declined surgery and the gelding was euthanased. Postmortem examination confirmed a diagnosis of cutaneous mastocytoma and revealed eosinophilic infiltration of the small intestine.


2020 ◽  
Vol 318 (1) ◽  
pp. G99-G108 ◽  
Author(s):  
Marcello Costa ◽  
Timothy James Hibberd ◽  
Lauren J. Keightley ◽  
Lukasz Wiklendt ◽  
John W. Arkwright ◽  
...  

Cyclical propagating waves of muscle contraction have been recorded in isolated small intestine or colon, referred to here as motor complexes (MCs). Small intestinal and colonic MCs are neurogenic, occur at similar frequencies, and propagate orally or aborally. Whether they can be coordinated between the different gut regions is unclear. Motor behavior of whole length mouse intestines, from duodenum to terminal rectum, was recorded by intraluminal multisensor catheter. Small intestinal MCs were recorded in 27/30 preparations, and colonic MCs were recorded in all preparations ( n = 30) with similar frequencies (0.54 ± 0.03 and 0.58 ± 0.02 counts/min, respectively). MCs propagated across the ileo-colonic junction in 10/30 preparations, forming “full intestine” MCs. The cholinesterase inhibitor physostigmine increased the probability of a full intestine MC but had no significant effect on frequency, speed, or direction. Nitric oxide synthesis blockade by Nω-nitro-l-arginine, after physostigmine, increased MC frequency in small intestine only. Hyoscine-resistant MCs were recorded in the colon but not small intestine ( n = 5). All MCs were abolished by hexamethonium ( n = 18) or tetrodotoxin ( n = 2). The enteric neural mechanism required for motor complexes is present along the full length of both the small and large intestine. In some cases, colonic MCs can be initiated in the distal colon and propagate through the ileo-colonic junction, all the way to duodenum. In conclusion, the ileo-colonic junction provides functional neural continuity for propagating motor activity that originates in the small or large intestine. NEW & NOTEWORTHY Intraluminal manometric recordings revealed motor complexes can propagate antegradely or retrogradely across the ileo-colonic junction, spanning the entire small and large intestines. The fundamental enteric neural mechanism(s) underlying cyclic motor complexes exists throughout the length of the small and large intestine.


2020 ◽  
Vol 88 (6) ◽  
Author(s):  
Zhi Huo ◽  
Conghui He ◽  
Ying Xu ◽  
Tianjun Jia ◽  
Jie Wang ◽  
...  

ABSTRACT The cryptic plasmid pCM is critical for chlamydial colonization in the gastrointestinal tract. Nevertheless, orally inoculated plasmid-free Chlamydia sp. was still able to colonize the gut. Surprisingly, orally inoculated Chlamydia sp. deficient in only plasmid-encoded pGP3 was no longer able to colonize the gut. A comparison of live organism recoveries from individual gastrointestinal tissues revealed that pGP3-deficient Chlamydia sp. survived significantly better than plasmid-free Chlamydia sp. in small intestinal tissues. However, the small intestinal pGP3-deficient Chlamydia sp. failed to reach the large intestine, explaining the lack of live pGP3-deficient Chlamydia sp. in rectal swabs following an oral inoculation. Interestingly, pGP3-deficient Chlamydia sp. was able to colonize the colon following an intracolon inoculation, suggesting that pGP3-deficient Chlamydia sp. might be prevented from spreading from the small intestine to the large intestine. This hypothesis is supported by the finding that following an intrajejunal inoculation that bypasses the gastric barrier, pGP3-deficient Chlamydia sp. still failed to reach the large intestine, although similarly inoculated plasmid-free Chlamydia sp. was able to do so. Interestingly, when both types of organisms were intrajejunally coinoculated into the same mouse small intestine, plasmid-free Chlamydia sp. was no longer able to spread to the large intestine, suggesting that pGP3-deficient Chlamydia sp. might be able to activate an intestinal resistance for regulating Chlamydia sp. spreading. Thus, the current study has not only provided evidence for reconciling a previously identified conflicting phenotype but also revealed a potential intestinal resistance to chlamydial spreading. Efforts are under way to further define the mechanism of the putative intestinal resistance.


2005 ◽  
Vol 145 (8) ◽  
pp. 1017-1026 ◽  
Author(s):  
Ahmed F El-Yazbi ◽  
Woo-Jung Cho ◽  
Geoffrey Boddy ◽  
Edwin E Daniel

2006 ◽  
Vol 290 (2) ◽  
pp. G394-G403 ◽  
Author(s):  
Ahmed F. El-Yazbi ◽  
Woo Jung Cho ◽  
Geoffrey Boddy ◽  
Richard Schulz ◽  
Edwin E. Daniel

Recently, we showed that caveolin-1 (cav1) knockout mice (Cav1−/− mice) have impaired nitric oxide (NO) function in the longitudinal muscle (LM) layer of the small intestine. The defect was a reduced responsiveness of the muscles to NO compensated by an increase in the function of apamin-sensitive, nonadrenergic, noncholinergic (NANC) mediators. In the present study, we examined similarly the effects of cav1 knockout on the relaxation in circular muscle (CM) of the mouse small intestine. CM of Cav1−/− mice also showed defective NO function, but less than in LM, as well as more activation of apamin-sensitive NANC mediators. CM of Cav1−/− mice, like LM, lacked cav1 but retained small amounts of cav3 and caveolae in the outer CM layer. In addition, we also examined the effects of a soluble guanylate cyclase inhibitor, 1 H-[1,2,4]oxadiazolo-[4,3-α]quinazolin-1-one (ODQ), on electric field stimulation (EFS)-mediated relaxation in both LM and CM. ODQ had an effect similar to the block of NO synthesis. Moreover, we compared the actions of two NO donors in the LM and CM of control and Cav1−/− mice. Similar to LM, CM of Cav1−/− mice showed a reduced responsiveness to the NO donors sodium nitroprusside and S-nitroso- N-acetyl penicillamine. However, both ODQ and apamin blocked the inhibitory effects of the NO donors in LM, whereas apamin had no effect in CM. In conclusion, cav1 knockout affects NO function in both LM and CM, but its effects in CM differ significantly.


2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Ahmed Fawzy El‐Yazbi ◽  
Richard Schulz ◽  
Edwin Daniel

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Ahmed El‐Yazbi ◽  
Woo Jung Cho ◽  
Johnathan Cena ◽  
Richard Schulz ◽  
Edwin Daniel

2008 ◽  
Vol 12 (4) ◽  
pp. 1404-1415 ◽  
Author(s):  
Ahmed F. El-Yazbi ◽  
Woo Jung Cho ◽  
Jonathan Cena ◽  
Richard Schulz ◽  
Edwin E. Daniel

2008 ◽  
Vol 294 (6) ◽  
pp. G1335-G1343 ◽  
Author(s):  
Katrine T.-B. G. Schjoldager ◽  
Henrik R. Maltesen ◽  
Sophie Balmer ◽  
Leif R. Lund ◽  
Mogens H. Claesson ◽  
...  

During the early postnatal period lymphocytes migrate into the mouse small intestine. Migrating infiltrative lymphocytes have the potential to affect the epithelial cells via secreted cytokines. Such cross talk can result in the elicitation of an epithelial transcriptional response. Knowledge about such physiological cross talk between the immune system and the epithelium in the postnatal small intestinal mucosa is lacking. We have investigated the transcriptome changes occurring in the postnatal mouse small intestine using DNA microarray technology, immunocytochemistry, and quantitative real-time RT-PCR analysis. The DNA microarray data were analyzed bioinformatically by using a combination of projections to latent structures analysis and functional annotation analysis. The results show that infiltrating lymphocytes appear in the mouse small intestine in the late postweaning period and give rise to distinct changes in the epithelial transcriptome. Of particular interest is the expression of three genes encoding a mucin ( Muc4), a mucinlike protein ( 16000D21Rik), and ATP citrate lyase (Acly). All three genes were shown to be expressed by the epithelium and to be upregulated in response to lymphocytic migration into the small intestinal mucosa.


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