Videoimaging of prostatic stromal‐cell contraction: An in vitro model for studying drug effects

Corvin, Stefan; Bösch, Simone T.; Eder, Iris E.; Thurnher, Martin; Bartsch, Georg; Klocker, Helmut

doi:10.1002/(sici)1097-0045(19981201)37:4<209::aid-pros1>3.3.co;2-l

Cited by 8 publications

(11 citation statements)

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“…Namely, that HCPSC express functional α 1 ‐adrenoceptors capable of mediating cellular contraction, and that such contractile responses are blocked by α 1 ‐adrenoceptor selective antagonists (Preston & Haynes, 2003), by L‐type Ca 2+ channel blockers ( Haynes et al , 2001 ; Preston & Haynes, 2003) and by activation of K + channels ( Cook et al , 2002 ). These findings are consistent with studies of human acutely dissociated and cultured prostatic stromal cells ( Eckert et al , 1995 ; Corvin et al , 1998 ) and whole tissue ( Hieble et al , 1985 ; Lepor et al , 1991 ; Lepor et al , 1993 ; Marshall et al , 1995 ).…”

Section: Introductionsupporting

confidence: 90%

A₁ and A_2A adenosine receptor modulation of α₁‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

Preston

Frydenberg

Haynes³

2004

British J Pharmacology

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This study investigated the possibility that adenosine receptors modulate the α1‐adrenoceptor‐mediated contractility of human cultured prostatic stromal cells (HCPSC). The nonselective adenosine receptor agonist, 5′‐N‐ethylcarboxamido‐adenosine (NECA; 10 nM–10 μM), and the A1 adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nM–10 μM), elicited significant contractions in HCPSC, with maximum contractile responses of 18±3% and 17±2% reduction in initial cell length, respectively. In the presence of a threshold concentration of phenylephrine (PE) (100 nM), CPA (1 nM–10 μM) caused contractions, with an EC50 of 124±12 nM and maximum contractile response of 37±4%. The A1 adenosine receptor‐selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX 100 nM) blocked this effect. In the presence of DPCPX (100 nM), NECA (1 nM–10 μM) inhibited contractions elicited by a submaximal concentration of PE (10 μM), with an IC50 of 48±2 nM. The A2A adenosine receptor‐selective antagonist 4‐(2‐[7‐amino‐2‐{furyl}{1,2,4}triazolo{2,3‐α}{1,3,5,}triazin‐5‐yl amino]ethyl)phenol (Zm241385 100 nM) blocked this effect. In BCECF‐AM (10 μM)‐loaded cells, both CPA (100 pM–1 μM) and NECA (100 pM–10 μM) elicited concentration‐dependent decreases in intracellular pH (pHi), with EC50 values of 3.1±0.3 and 6.0±0.3 nM, respectively. The response to NECA was blocked by Zm241385 (100 nM; apparent pKB of 9.4±0.4), but not by DPCPX (100 nM). The maximum response to CPA was blocked by DPCPX (100 nM), and unaffected by Zm241385 (100 nM). NECA (10 nM–10 μM) alone did not increase [3H]‐cAMP in HCPSC. In the presence of DPCPX (100 nM), NECA (10 nM–10 μM) caused a concentration dependent increase in [3H]‐cAMP, with an EC50 of 1.2±0.1 μM. This response was inhibited by Zm241385 (100 nM). CPA (10 nM–10 μM) had no effect on cAMP, in the presence or absence of forskolin (1 μM). These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor‐mediated contractility in human prostate‐derived cells. British Journal of Pharmacology (2004) 141, 302–310. doi:

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Section: Introductionsupporting

confidence: 90%

A₁ and A_2A adenosine receptor modulation of α₁‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

Preston

Frydenberg

Haynes³

2004

British J Pharmacology

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“… Primary cultures of prostatic cells were derived from specimens obtained on radical prostatectomy. The cells were cultured following protocols published previously15–18. IL‐6 in the supernatants was determined by ELISA. …”

Section: Resultsmentioning

confidence: 99%

“…The assay was performed according to the manufacturer's instructions. Stromal cells, including both fibroblasts and smooth muscle cells, and epithelial cells were cultured as described previously15–18. The functionality of these cultured stromal cells has been described in a previous publication18.…”

Section: Methodsmentioning

confidence: 99%

Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue

et al. 2000

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Interleukin-6 (IL-6) is a pleiotropic cytokine that interacts with its receptor in prostate cells, thus regulating proliferative response and differentiation. It also activates the human androgen receptor in prostate cancer cell lines. In order to assess the significance of these findings in vivo, the expression of key elements of the IL-6 signalling pathway, IL-6 and its receptor, was investigated in tissue samples obtained on radical prostatectomy from prostate cancer patients. IL-6 immunohistochemistry was performed on 17 frozen prostate cancer specimens. IL-6 receptor immunostaining was evaluated in 21 paraffin-embedded prostate tumour specimens. In both groups, adjacent areas of high-grade prostatic intraepithelial neoplasia and benign tissue were also investigated. In benign prostatic epithelium, IL-6 was localized predominantly in basal cells, whereas in prostate cancer tissues more IL-6-positive glandular cells were identified. No IL-6 expression was detected in stromal cells on immunohistochemistry, although IL-6 protein was measured in the supernatants obtained from cultured stromal cells by ELISA. IL-6 receptor was expressed in benign prostatic tissue in both epithelial and stromal cells. Furthermore, IL-6 receptor expression was observed in all tumour specimens investigated and the majority of Gleason patterns analysed had more than 50% of cells showing a positive reaction. IL-6 and IL-6 receptor expression patterns in high-grade prostatic intraepithelial neoplasia lesions were similar to those observed in tumour tissues. Taken together, the results of the present study imply that there are paracrine and autocrine IL-6 loops in benign and neoplastic prostate.

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“…Most functional in vitro studies have focused on prostate contraction. This has been assessed by videoimaging of human prostatic stromal cell contractions in the presence of α 1 ‐adrenoceptor agonists and antagonists in some cases (Corvin et al ., 1998), but the vast majority of studies has used classical organ bath approaches with prostatic strips from various species. α‐Adrenoceptor‐mediated contraction of the prostate of rabbits (Honda et al ., 1985), dogs (Felsen et al ., 1994; Delaflotte et al ., 1996) and humans (Hieble et al ., 1985; Lepor et al ., 1988b; Chapple et al ., 1989; Yu et al ., 1994) appears to occur largely, if not exclusively, via α 1 ‐ rather than α 2 ‐adrenoceptors; such findings have been obtained by comparing the effects of α 1 ‐selective agonists such as phenylephrine with those of α 2 ‐selective agonists such as UK 14,304, or by comparing the antagonism of noradrenaline by α 1 ‐selective antagonists such as prazosin with that of α 2 ‐selective antagonists such as rauwolscine.…”

Section: Prostatementioning

confidence: 99%

α₁‐, α₂‐ and β‐adrenoceptors in the urinary bladder, urethra and prostate

Michel

Vrydag

2006

British J Pharmacology

413

320

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1 We have systematically reviewed the presence, functional responses and regulation of a 1 -, a 2 -and b-adrenoceptors in the bladder, urethra and prostate, with special emphasis on human tissues and receptor subtypes. 2 a 1 -Adrenoceptors are only poorly expressed and play a limited functional role in the detrusor. a 1 -Adrenoceptors, particularly their a 1A -subtype, show a more pronounced expression and promote contraction of the bladder neck, urethra and prostate to enhance bladder outlet resistance, particularly in elderly men with enlarged prostates. a 1 -Adrenoceptor agonists are important in the treatment of symptoms of benign prostatic hyperplasia, but their beneficial effects may involve receptors within and outside the prostate. 3 a 2 -Adrenoceptors, mainly their a 2A -subtype, are expressed in bladder, urethra and prostate. They mediate pre-junctional inhibition of neurotransmitter release and also a weak contractile effect in the urethra of some species, but not humans. Their overall post-junctional function in the lower urinary tract remains largely unclear. 4 b-Adrenoceptors mediate relaxation of smooth muscle in the bladder, urethra and prostate. The available tools have limited the unequivocal identification of receptor subtypes at the protein and functional levels, but it appears that the b 3 -and b 2 -subtypes are important in the human bladder and urethra, respectively. b 3 -Adrenoceptor agonists are promising drug candidates for the treatment of the overactive bladder. 5 We propose that the overall function of adrenoceptors in the lower urinary tract is to promote urinary continence. Further elucidation of the functional roles of their subtypes will help a better understanding of voiding dysfunction and its treatment.

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Videoimaging of prostatic stromal‐cell contraction: An in vitro model for studying drug effects

Cited by 8 publications

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A₁ and A_2A adenosine receptor modulation of α₁‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

A₁ and A_2A adenosine receptor modulation of α₁‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue

α₁‐, α₂‐ and β‐adrenoceptors in the urinary bladder, urethra and prostate

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Videoimaging of prostatic stromal‐cell contraction: An in vitro model for studying drug effects

Cited by 8 publications

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A1 and A2A adenosine receptor modulation of α1‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

A1 and A2A adenosine receptor modulation of α1‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue

α1‐, α2‐ and β‐adrenoceptors in the urinary bladder, urethra and prostate

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A₁ and A_2A adenosine receptor modulation of α₁‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

A₁ and A_2A adenosine receptor modulation of α₁‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells

α₁‐, α₂‐ and β‐adrenoceptors in the urinary bladder, urethra and prostate