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The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types.

Publication ,  Journal Article
Tseng-Crank, J; Kost, T; Goetz, A; Hazum, S; Roberson, KM; Haizlip, J; Godinot, N; Robertson, CN; Saussy, D
Published in: Br J Pharmacol
August 1995

1. Benign prostatic hyperplasia (BPH) causes urinary obstruction in aging men that frequently requires surgery to relieve the symptoms of urinary retention, nocturia, and micturition. Smooth muscle tone which contributes to the urethral constriction in the enlarged gland appears to be mediated by the alpha 1-adrenoceptors. In this paper, molecular and pharmacological approaches are used to establish the role played by the alpha 1C-adrenoceptor subtype in the prostate. 2. The alpha 1-adrenoceptor subtype(s) expressed in human prostate were investigated by use of polymerase chain reaction (PCR), Northern blot, and in situ hybridization. The alpha 1C subtype was found in both prostate stromal and glandular cells while alpha 1B and alpha 1D subtypes were expressed in glandular cells. High expression levels for alpha 1C were observed in prostate cancer tissues in both stroma and glandular cells. 3. Full length alpha 1C-adrenoceptor cDNA was cloned from human prostate. Stable mammalian cell lines expressing human alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptors were made. Membranes prepared from these cell lines and human prostate were used to evaluate the pharmacological profiles of human alpha 1B-, alpha 1C- and alpha 1D-adrenoceptors in comparison to human prostate. Leverage plot analysis of compound affinities determined by competition for [125I]-I-HEAT binding demonstrated that the alpha 1C subtype is the predominant alpha 1-adrenoceptor in human prostate. 4. The alpha 1-adrenoceptors cause smooth muscle constriction by coupling to IP3 turnover and intracellular Ca2+ release. Using stable cell lines to measure IP3 production in response to noradrenaline, alpha 1C stimulated IP3 production most efficiently, with alpha 1B at an intermediate level, while little IP3 above background could be detected with alpha 1D. These results supported a functional role of the alpha 1C-adrenoceptor on prostate smooth muscle constriction by noradrenaline stimulation.

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Published In

Br J Pharmacol

DOI

ISSN

0007-1188

Publication Date

August 1995

Volume

115

Issue

8

Start / End Page

1475 / 1485

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Restriction Mapping
  • Receptors, Adrenergic, alpha-2
  • Rats
  • Prostatic Neoplasms
  • Prostatic Hyperplasia
  • Prostate
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Pharmacology & Pharmacy
 

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Tseng-Crank, J., Kost, T., Goetz, A., Hazum, S., Roberson, K. M., Haizlip, J., … Saussy, D. (1995). The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br J Pharmacol, 115(8), 1475–1485. https://doi.org/10.1111/j.1476-5381.1995.tb16640.x
Tseng-Crank, J., T. Kost, A. Goetz, S. Hazum, K. M. Roberson, J. Haizlip, N. Godinot, C. N. Robertson, and D. Saussy. “The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types.Br J Pharmacol 115, no. 8 (August 1995): 1475–85. https://doi.org/10.1111/j.1476-5381.1995.tb16640.x.
Tseng-Crank J, Kost T, Goetz A, Hazum S, Roberson KM, Haizlip J, et al. The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br J Pharmacol. 1995 Aug;115(8):1475–85.
Tseng-Crank, J., et al. “The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types.Br J Pharmacol, vol. 115, no. 8, Aug. 1995, pp. 1475–85. Pubmed, doi:10.1111/j.1476-5381.1995.tb16640.x.
Tseng-Crank J, Kost T, Goetz A, Hazum S, Roberson KM, Haizlip J, Godinot N, Robertson CN, Saussy D. The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br J Pharmacol. 1995 Aug;115(8):1475–1485.
Journal cover image

Published In

Br J Pharmacol

DOI

ISSN

0007-1188

Publication Date

August 1995

Volume

115

Issue

8

Start / End Page

1475 / 1485

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Restriction Mapping
  • Receptors, Adrenergic, alpha-2
  • Rats
  • Prostatic Neoplasms
  • Prostatic Hyperplasia
  • Prostate
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Pharmacology & Pharmacy