title: [Acetylcholine induces human detrusor muscle cell proliferation: molecular and pharmacological characterization].
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cattedra di Urologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Brescia, Brescia, Italy. dr.arrighi@live.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Arrighi
authors.forename: Serena
authors.initials: S
authors.lastname: Bodei
authors.forename: Danilo
authors.initials: D
authors.lastname: Zani
authors.forename: Claudio
authors.initials: C
authors.lastname: Simeone
authors.forename: Sergio Cosciani
authors.initials: SC
authors.lastname: Cunico
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Spano
authors.forename: Sandra
authors.initials: S
authors.lastname: Sigala
mesh_terms: D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000368:Aged; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D001743:Urinary Bladder / Q000187:drug effects*
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; D000109:Acetylcholine; C048593:otenzepad