Alpha<sub>1</sub>‐adrenoceptor subtypes in the human prostate

Chapple, Christopher R.; Burt, Richard P.; Andersson, Per‐Olof; Greengrass, Pamela M.; Wyllie, Michael G.; Marshall, Ian

doi:10.1111/j.1464-410x.1994.tb09188.x

Cited by 82 publications

(51 citation statements)

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“…Four subtypes of α1-ARs (α1A, α1B, α1C, and α1L) have been identified in human prostate cells (7)(8)(9)(10)(11). These receptors are mostly localized in the fibromuscular stroma, where they mediate the contraction of prostate smooth muscle (8).…”

Section: Discussionmentioning

confidence: 99%

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α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Thebault¹,

Roudbaraki²,

Sydorenko³

et al. 2003

J. Clin. Invest.

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. Y. Shuba's present address is: Bogomoletz Institute of Physiology, Kiev, Ukraine. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: α1-adrenergic receptor (α1-AR); human prostate cancer epithelial cell (hPCE cell); phospholipase C (PLC); inositol triphosphate (IP3); diacylglycerol (DAG); transient receptor potential (TRP); α1A subtype of α1-AR (α1A-AR); lymph node carcinoma of the prostate cells (LNCaP cells); intracellular Ca 2+ concentration ([Ca 2+ ]i); phenylephrine (Phe); intracellular Ca 2+ oscillations (osc); 2-aminophenyl borate (2-APB); store-operated Ca 2+ -channel (SOC); 1-oleoyl-2-acetyl-snglycerol (OAG); 1,2-dioctanoyl-sn-glycerol (DOG); extracellular Ca 2+ concentration ([Ca 2+ ]out); Phe-activated current (IPhe); current reversal potential (Erev).

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Section: Discussionmentioning

confidence: 99%

“…Among α1-AR subtypes, α1A is believed to be predominant in the fibromuscular stroma of the prostate (7)(8)(9)(10)(11). Its stimulation leads principally to the activation of phospholipase C (PLC), ultimately resulting in an increase in intracellular free Ca 2+ via inositol triphosphate (IP 3 ) and diacylglycerol (DAG) production (12,13).…”

Section: Introductionmentioning

confidence: 99%

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Thebault¹,

Roudbaraki²,

Sydorenko³

et al. 2003

J. Clin. Invest.

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“…The al-adrenoceptor subtypes expressed in human prostate have been pharmacologically characterized by radioligand binding assay (Muramatsu et al, 1994;Chapple et al, 1994) and the'expression of the three subtype mRNAs has been examined by an RNase protection assay and in situ hybridization (Price et al, 1993b;Moriyama et al, 1996 (Price et al, 1993b;Moriyama et al, 1996). However, we found a major difference between BPH and non-BPH samples: the total abundance of xl-adrenoceptor mRNA in BPH samples was over six times that in non-BPH samples, and the abundance of axl a mRNA in BPH samples was almost nine times that in non-BPH samples.…”

Section: Discussionmentioning

confidence: 99%

Quantification and distribution of α1‐adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non‐hypertrophied tissue

Nasu

Moriyama

Kawabe

et al. 1996

British J Pharmacology

160

127

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1 There are at least three cxl-adrenoceptor subtypes, cxla, alb and ald, in human tissues. Using an RNase protection assay, we have now determined the amount of each subtype mRNA in human prostatic tissue, for both benign prostatic hypertrophy (BPH) and non-BPH. In all tissue samples examined, the predominant subtype mRNA was ala. The total abundance of al-adrenoceptor mRNA in BPH samples was over six times that in non-BPH samples. This increase was mostly accounted for by ala, which was almost nine times as abundant in BPH samples as in non-BPH samples. The abundance of alb was almost the same between BPH and non-BPH samples, and the abundance of ald in BPH samples was about three times that in non-BPH samples. The ratio of the numbers of the subtype mRNAs, ala: alb: ald, was 85:1:14 in BPH samples and 63 :6:31 in non-BPH samples. 2 In situ hybridization studies showed no significant differences in the tissue localization of Lxladrenoceptor subtype mRNAs between BPH and non-BPH samples. atla and acld were clearly detected in the interstitium of the prostate, where axla was stained more intensely than Lxld, and the positive sites were primarily smooth muscle cells. In contrast, alb staining was very faint. 3 This increase in mRNA abundance may be directly related to the contraction of prostatic tissue that leads to obstruction of the urinary tract in BPH patients. Specifically, our data suggest that increased expression of the Lxla subtype may be primarily responsible for the contraction of the prostate.

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“…The proposition that a given adrenoceptor subtype may be responsible for the contractility of prostatic and urethral smooth muscle cells led to the concept that drugs selective for this subtype may exhibit functional uroselectivity [7]. In the human prostate, the three cloned subtypes have been identified and the α 1a/A -adrenoceptor subtype has been described to be the most abundant receptor subtype in prostatic smooth muscle [8, 9].…”

Section: Is Affinity or Selectivity For An α1-adrenoceptor Subtype Prmentioning

confidence: 99%

Functional Uroselectivity

Martin¹,

Angel²,

Arbilla³

1998

Eur Urol

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α₁-Adrenoceptors mediating sympathetic tone to smooth muscle cells are located within the prostatic tissue, bladder base and in the proximal urethra, but are also widely distributed within a large number of tissues, especially the vascular beds and the central nervous system. Compounds clinically used in the symptomatic treatment of benign prostatic hyperplasia must therefore exhibit functional uroselectivity. This means that they should preferentially act on the lower urinary tract rather than the vasculature or central nervous system. Few clinically used α₁-adrenoceptor antagonists show selectivity for the α_1a/A-adrenoceptor subtype, whereas most of them have similar affinities for the three cloned subtypes (α_1a-, α_1b- and α_1d-adrenoceptors). Recent data from in vitro studies assessing pharmacological uroselectivity and from in vivo models evaluating functional uroselectivity challenged the relevance of the affinity or the selectivity for a known α₁-adrenoceptor subtype in predicting functional uroselectivity. They suggest instead that another subtype, like the α_1L-adrenoceptor, might be functionally involved. In conclusion, the actual state of knowledge on α₁-adrenoceptor subtype distribution and function, does not support a role of pharmacological uroselectivity in predicting functional uroselectivity. Furthermore, functional uroselectivity can be achieved in the absence of selectivity for the α₁-adrenoceptor subtypes described so far.

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Alpha₁‐adrenoceptor subtypes in the human prostate

Cited by 82 publications

References 6 publications

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Quantification and distribution of α1‐adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non‐hypertrophied tissue

Functional Uroselectivity

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Alpha1‐adrenoceptor subtypes in the human prostate

Cited by 82 publications

References 6 publications

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Quantification and distribution of α1‐adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non‐hypertrophied tissue

Functional Uroselectivity

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Alpha₁‐adrenoceptor subtypes in the human prostate