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Acetylcholine induces human detrusor muscle cell proliferation: molecular and pharmacological characterization

Abstract

Introduction: The purpose of the study is to understand whether the cholinergic stimulation is important, not only in inducing contraction of the detrusor muscle, but also in modulating the proliferation of smooth muscle cells. These results could help to better understand the role of antimuscarinic drugs, which are currently used for the treatment of many urological diseases.
Patients and methods: Primary cultures were prepared from biopsies of human detrusor muscle of subjects >65 years. From the cell culture set-up for each patient, mRNA was extracted and both the gene expression and the influence of increasing passages on the expression of muscarinic receptor subtypes were evaluated by semi-quantitative and quantitative PCR (RT-PCR and Q-RT-PCR). The rate of cell proliferation induced by cholinergic drugs was assessed by the evaluation of the [3H]-thymidine incorporation.
Results: The gene expression analysis demonstrated that the range of expression of muscarinic subtypes in human detrusor smooth muscle cells (HDSMCs) is M2 > M3 > M1 > M4 >> M5. The exposure to the cholinergic agonist carbachol induced a concentration-dependent increase in cell proliferation rate. The pharmacological characterization indicated that this effect was mainly mediated by the receptor subtypes M3 and M2.
Discussion: The cholinergic stimulation led to an increase in HDSMC proliferation, suggesting that this phenomenon might be involved in the pathogenic mechanism through which the cervico-urethral obstruction causes a detrusor hypertrophy, followed by a loss of function. These results could then provide an indication of the use of antimuscarinic drugs in the treatment of lower urinary tract disorders.

Urologia 2012; 79(2): 102 - 108

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/RU.2012.9272

Authors

Nicola Arrighi, Serena Bodei, Danilo Zani, Claudio Simeone, Sergio Cosciani Cunico, Pier Franco Spano, Sandra Sigala

Article History

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Authors

  • Arrighi, Nicola [PubMed] [Google Scholar]
    Cattedra di Urologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia - Italy
  • Bodei, Serena [PubMed] [Google Scholar]
    Sezione di Farmacologia, Dipartimento di Scienze Biomediche e Biotecnologie, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia
  • Zani, Danilo [PubMed] [Google Scholar]
    Cattedra di Urologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia - Italy
  • Simeone, Claudio [PubMed] [Google Scholar]
    Cattedra di Urologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia - Italy
  • Cunico, Sergio Cosciani [PubMed] [Google Scholar]
    Cattedra di Urologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia - Italy
  • Spano, Pier Franco [PubMed] [Google Scholar]
    Sezione di Farmacologia, Dipartimento di Scienze Biomediche e Biotecnologie, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia
  • Sigala, Sandra [PubMed] [Google Scholar]
    Sezione di Farmacologia, Dipartimento di Scienze Biomediche e Biotecnologie, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia

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