Ureterovesical junction obstruction causes increment in smooth muscle contractility, and cholinergic and adrenergic activity in distal ureter of rabbits

Ertunç, Mert; Ardicli, Burak; Kabakus, Ismail; Tas, Taskin S.; Sara, Yıldırım; Onur, Rüştü; Karnak, İbrahìm

doi:10.1016/j.jpedsurg.2013.01.030

Cited by 10 publications

(12 citation statements)

References 40 publications

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“…In the current study, similarly, 5-HT induced concentration-dependent increases in contractile activity, increasing both the frequency and magnitude of phasic contractions in distal ureters from older and younger pigs. This is in agreement with most other findings in tissues from pig and human (Gidener et al, 1999;Gidener et al, 1995;Hernandez et al, 2003), but contrasts with a study in rabbit isolated tissues that failed to find any ureteral response to 5-HT, suggesting that these responses are species dependent and the pig represents a good model for human (Yalcin et al, 2013).…”

Section: Discussionsupporting

confidence: 89%

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5-HT2A receptor is the predominant receptor mediating contraction of the isolated porcine distal ureter to 5-HT in young and old animals

Lim

Chess-Williams

Sellers

2018

European Journal of Pharmacology

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Isolated ureteral strips develop spontaneous phasic contractile activity which is enhanced by 5-hydroytryptamine (5-HT). The aim of this study was to identify the receptor subtype mediating these responses and to determine whether responses to 5-HT change with age. The frequency of contractions and the overall contractile activity (measured as the area under the curve, AUC) were recorded in strips of porcine distal ureter isolated from young (3 months) and old (2 years) pigs. Responses to 5-HT were examined in the absence and presence of selective 5-HT receptor subtype antagonists. Tissues from the younger animals elicited larger contractile responses to 5-HT (5885 ± 335g s) than tissues from the older animals (2787 ± 317g s, P < 0.001). The 5-HT receptor antagonist ketanserin (10-100nM) elicited rightward shifts of 5-HT concentration-response curves, antagonising AUC and frequency responses with high affinity in tissues from both age groups (pK values 8.4-8.8). The slopes of the corresponding Schild plots were not significantly different from unity, suggesting a competitive antagonism at a single receptor, except for frequency responses to 5-HT in the older animals. Antagonists selective for other 5-HT receptor subtypes: methiothepin (non-selective), RS-10221 (5-HT), ondansetron (5-HT), GR-113808 (5-HT), SB699551 (5-HT), SB39988 (5-HT), SB269970 (5-HT)) had no effect on 5-HT-induced responses. The results suggest that the 5-HT receptor subtype is the predominant receptor mediating 5-HT responses in ureteral tissues, being the sole mediator of responses in tissues from young animals, but with another receptor subtype also playing a minor role in the older animals.

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Section: Discussionsupporting

confidence: 89%

“…Furthermore, an upregulation of 5-HT2A receptors may occur during obstruction and in the rabbit ureter it has been shown that 5-HT-stimulated contractile responses are enhanced in the presence of ureteral obstruction (Yalcin et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

5-HT2A receptor is the predominant receptor mediating contraction of the isolated porcine distal ureter to 5-HT in young and old animals

Lim

Chess-Williams

Sellers

2018

European Journal of Pharmacology

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“…HCN3+ and cKIT+ populations of utPMCs function sequentially to initiate and propagate pyeloureteric contractions. 2,3,5 Although the presence and spatial organization of utPMCs has been shown to be perturbed in congenital urinary tract malformations and particularly in hydronephrosis, 18,[23][24][25][26][27][28][29][30][31][32][33][34] little is known regarding the direct contribution of utPMCs to the pathobiology of these disorders. Lack of knowledge regarding the origin and development of utPMCs limits the ability to investigate these issues.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas the expression of HCN3 has not been analyzed, cKIT expression is altered in ureteric tissue isolated from humans and experimental animals with congenital kidney diseases, including vesicoureteral reflux, ureteropelvic junction (UPJ) obstruction, primary obstructive megaureter, and nonobstructive hydronephrosis. [23][24][25][26][27][28][29][30][31][32][33][34] Analysis of proximal ureter tissue sections from children with UPJ obstruction undergoing pyeloplasty demonstrated decreased cKIT expression, 24,29,31 although primary obstructive megaureter tissues also exhibit significantly fewer cKIT+ cells compared with control samples. 30,33 The critical contribution of HCN3+ and cKIT+ utPMCs to urinary tract health and perturbation of these cells in congenital kidney diseases provides an impetus to elucidate mechanisms that control the specification and differentiation of these cells.…”

Section: Significance Statementmentioning

confidence: 99%

Protein Kinase 2β Is Expressed in Neural Crest-Derived Urinary Pacemaker Cells and Required for Pyeloureteric Contraction

Iskander

Feeney

Yee

et al. 2018

JASN

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Nonobstructive hydronephrosis, defined as dilatation of the renal pelvis with or without dilatation of the ureter, is the most common antenatal abnormality detected by fetal ultrasound. Yet, the etiology of nonobstructive hydronephrosis is poorly defined. We previously demonstrated that defective development of urinary tract pacemaker cells (utPMCs) expressing hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) and the stem cell marker cKIT causes abnormal ureteric peristalsis and nonobstructive hydronephrosis. However, further investigation of utPMC development and function is limited by lack of knowledge regarding the embryonic derivation, development, and molecular apparatus of these cells. Here, we used lineage tracing in mice to identify cells that give rise to utPMCs. Neural crest cells (NCCs) indelibly labeled with tdTomato expressed HCN3 and cKIT. Furthermore, purified HCN3+ and cKIT+ utPMCs were enriched in and, markers of NCCs. Sequencing of purified RNA from HCN3+ cells revealed enrichment of a small subset of RNAs, including RNA encoding protein kinase 2 (PTK2), a Ca-dependent tyrosine kinase that regulates ion channel activity in neurons. Immunofluorescence analysis revealed PTK2 expression in NCCs as early as embryonic day 12.5 and in HCN3+ and cKIT+ utPMCs as early as embryonic day 15.5, with sustained expression in HCN3+ utPMCs until postnatal week 8. Pharmacologic inhibition of PTK2 in murine pyeloureteral tissue explants inhibited contraction frequency. Together, these results demonstrate that utPMCs are derived from NCCs, identify new markers of utPMCs, and demonstrate a functional contribution of PTK2 to utPMC function.

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“…The different course of natural history of this entity associated with different imaging characters has caused dilemma in the presentation, differential diagnosis, and decision making for its management. UVJO causes increment in smooth muscle contractility as well as in cholinergic and adrenergic activity in distal ureter of rabbits (3). UVJO may coexist with UPJO and this may cause a problem both in diagnosis and in management (4)(5)(6).…”

Section: Discussionmentioning

confidence: 99%

The Dilemma of Ureterovesical Junction Obstruction

Rabani

Mousavizadeh

2017

Nephro-Urol Mon

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Background: Ureterovesical junction obstruction (UVJO) is the result of an anatomic or a functional abnormality in the distal segment of the ureter. There are many types of UVJO, different in their cause, presentation, imaging characters, and prognosis. Objectives: The aim of this study was to discuss the postoperative natural course and prognosis of patients undergoing standard approaches on the management of primary UVJO by one surgeon in a 10-year period starting from 2004. Methods: From January 2004 to October 2013, 64 patients who underwent ureteral tapering and stenting ureteroneocystostomy for complicated primary UVJO participated in the study. Results: The mean age of patients was 26 years (range: 11 months to 73 years). The mean hospital stay was 5 days (range: 4 to 7 days). The post-operative time was between 1 and 2 hours. Double J stent was left in place for 4 weeks. Post-operative follow-up was at least one year. No major complication was encountered, instead, a decrease in symptoms in all patients and an increase in renal function in 40 out of 64 (62.5%) patients were observed in the one-year follow-up of the diethylenetriaminepentaacetic acid (DTPA) renal scanning. Only 3 patients had fever as a postoperative minor complication. Conclusions: Decision making in the treatment of UVJO is somewhat a dilemma. This condition is occasionally asymptomatic and uneventful, and may be detected accidentally during an unrelated work-up; nonetheless, it may also cause serious life threatening complications. Surgical management in complicated cases may be a safe and viable treatment option both in children and in adults.

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Ureterovesical junction obstruction causes increment in smooth muscle contractility, and cholinergic and adrenergic activity in distal ureter of rabbits

Cited by 10 publications

References 40 publications

5-HT2A receptor is the predominant receptor mediating contraction of the isolated porcine distal ureter to 5-HT in young and old animals

5-HT2A receptor is the predominant receptor mediating contraction of the isolated porcine distal ureter to 5-HT in young and old animals

Protein Kinase 2β Is Expressed in Neural Crest-Derived Urinary Pacemaker Cells and Required for Pyeloureteric Contraction

The Dilemma of Ureterovesical Junction Obstruction

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