Autoradiographic Localization of Tachykinin and Calcitonin Gene-Related Peptide Receptors in Adult Urinary Bladder

Burcher, Elizabeth; Zeng, Xiang‐Ping; Strigas, John; Shang, Fei; Millard, R. J.; Moore, Kate H.

doi:10.1097/00005392-200001000-00090

Cited by 11 publications

(15 citation statements)

References 30 publications

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“…The neuropeptides substance P (SP), neurokinin A (NKA) and neurokinin B have high affinity for NK 1 , NK 2 and NK 3 receptors, respectively, whereas the newly described haemokinin derived from inflammatory cells also has high affinity for NK 1 receptors ( Pennefather et al , 2004 ). NKA is coexpressed with SP and calcitonin gene‐related peptide in the capsaicin‐sensitive afferent fibres in the suburothelium and the detrusor of various species ( Smet et al , 1997 ), and their receptors are located on smooth muscle and blood vessels in the human bladder ( Burcher et al , 2000 ; Candenas et al , 2005 ). Tachykinin receptors are involved in the sensory mechanisms of micturition and are thought to relay information about bladder fullness, distension and visceral pain to the central nervous system ( Lecci and Maggi, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Contractile properties of the pig bladder mucosa in response to neurokinin A: a role for myofibroblasts?

Sadananda

Chess-Williams

Burcher

2008

British J Pharmacology

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Background and purpose: The bladder urothelium is now known to have active properties. Our aim was to investigate the contractile properties of the urinary mucosa in response to the tachykinin neurokinin A (NKA) and carbachol. Experimental approach: Discrete concentration-response curves for carbachol and NKA were obtained in matched strips of porcine detrusor, mucosa and intact bladder, suspended in organ baths. The effects of inhibitors and tachykinin receptor antagonists were studied on NKA-mediated contractions in mucosal strips. Intact sections of bladder and experimental strips were processed for histology and immunohistochemistry. Key results: All types of strips contracted to both carbachol and NKA. Mucosal responses to NKA (pD 2 7.2) were higher than those in intact strips and were inhibited by the NK 2 receptor antagonist SR48968 (pK B 9.85) but not the NK 1 receptor antagonist SR140333, tetrodotoxin or indomethacin. Immunostaining for smooth muscle actin and vimentin occurred under the urothelium and on blood vessels. Desmin immunostaining and histological studies showed only sparse smooth muscle to be present in the mucosal strips. Removal of smooth muscle remnants from mucosal strips did not alter the responses to NKA. Conclusions and implications:This study has shown both functional and histological evidence for contractile properties of the mucosa, distinct from the detrusor. Mucosal contractions to NKA appear to be directly mediated via NK 2 receptors. The main cell type mediating mucosal contractions is suggested to be suburothelial myofibroblasts. Mucosal contractions may be important in vivo for matching the luminal surface area to bladder volume.

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Section: Introductionmentioning

confidence: 99%

Contractile properties of the pig bladder mucosa in response to neurokinin A: a role for myofibroblasts?

Sadananda

Chess-Williams

Burcher

2008

British J Pharmacology

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“…17 In human urothelium, NK2R expression has not been detected, which is in contrast to animal studies, where NK2 receptors are present in rat urothelium and have a role initiating micturition. 18,19 The apparent species-specific differences in expression patterns of TK receptors warrant caution in interpreting the data obtained from animal models of BPS/IC, and prompted us to investigate the expression and localization of these receptors in healthy and diseased human bladders.…”

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confidence: 99%

MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome

Freire

Burkhard

Kessler

et al. 2010

The American Journal of Pathology

101

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Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability , bladder contractility , and inflammation , we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1 , junctional adherins molecule -1 , and occludin were similarly down-regulated , implicating increased urothelial permeability , whereas bradykinin B 1 receptor , cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cellbased models , we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients , the same miRNAs were significantly increased , suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b , miR-500 , miR-328 , and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS , and have relevance for other clinical conditions involving the NK1 receptor. (Am J

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“…The distribution of NK1 receptor in the oviduct and uterus resembles that described in other organs of laboratory animals. NK1 receptor was found in the vascular endothelium of the human urinary bladder (Burcher et al 2000) and lungs (Mechiche et al 2003). NK1 receptor was also found in the muscular membranes of the canine stomach and intestines (Mantyh et al 1988), as well as human colon (Korman et al 1989).…”

Section: Discussionmentioning

confidence: 99%

Expression of NK1 receptor at the protein and mRNA level in the porcine female reproductive system

Bukowski¹

2014

Polish Journal of Veterinary Sciences

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The presence and distribution of substance P (SP) receptor NK1 was studied in the ovary, the oviduct and the uterus (uterine horn and cervix) of the domestic pig using the methods of molecular biology (RT-PCR and immunoblot) and immunohistochemistry.The expression of NK1 receptor at mRNA level was confirmed with RT-PCR in all the studied parts of the porcine female reproductive system by the presence of 525 bp PCR product and at the protein level by the detection of 46 kDa protein band in immunoblot. Immunohistochemical staining revealed the cellular distribution of NK1 receptor protein. In the ovary NKI receptor was present in the wall of arterial blood vessels, as well as in ovarian follicles of different stages of development. In the tubular organs the NK1 receptor immunohistochemical stainings were observed in the wall of the arterial blood vessels, in the muscular membrane, as well as in the mucosal epithelium.The study confirmed the presence of NK1 receptor in the tissues of the porcine female reproductive tract which clearly points to the possibility that SP can influence porcine ovary, oviduct and uterus.

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Autoradiographic Localization of Tachykinin and Calcitonin Gene-Related Peptide Receptors in Adult Urinary Bladder

Cited by 11 publications

References 30 publications

Contractile properties of the pig bladder mucosa in response to neurokinin A: a role for myofibroblasts?

Contractile properties of the pig bladder mucosa in response to neurokinin A: a role for myofibroblasts?

MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome

Expression of NK1 receptor at the protein and mRNA level in the porcine female reproductive system

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