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Muscarinic receptor expression and receptor-mediated detrusor contraction: comparison of juvenile and adult porcine tissue

  • Gastrointestinal Function
  • Published:
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Abstract

Urinary bladder function is known to mature during fetal and postnatal development, including changes in neurotransmitter regulation of detrusor contraction. However, only few experimental data are available about muscarinic receptor antagonist function in the urinary bladder from young animals. In the present study, we compare the muscarinic receptor-mediated contractions in juvenile and adult porcine detrusor and the effects of antimuscarinic compounds. Urinary bladders from young (8–12 weeks; 12- to 35-kg body weight) and mature pigs (>40 weeks; >100 kg) were compared. Muscarinic receptor expression was assessed by real time polymerase chain reaction and radioligand binding. Muscle contraction was measured with a force transducer; L-type Ca2+ currents (I Ca,L) of isolated detrusor myocytes were recorded with standard voltage clamp technique. Juvenile and adult detrusor expressed similar quantities of the messenger RNA of M2 and M3 receptors. The number of [3H]QNB-binding sites and their affinity for the radioligand were also similar between juvenile and adult detrusor. In contrast, maximum contractile responses to the muscarinic receptor agonist carbachol were slightly larger in juvenile than adult bladders. On the other hand, carbachol was slightly less potent in juvenile than in adult tissue. The M3 antagonist DAU 5884 and the spasmolytic drug propiverine inhibited contractile responses with comparable efficacies and potencies in juvenile and adult tissue. I Ca,L was somewhat smaller in juvenile than in adult cells. Taken together, these data suggest that expression and function of M2 and M3 receptors are similar in the detrusor of juvenile and mature pigs. Therefore, similar responses to antimuscarinic compounds could be expected in young and adult patients.

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Acknowledgment

The authors would like to thank Sabine Kirsch and Martina Michel-Reher for their technical assistance.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Medical Faculty, Dresden University of Technology, Fetscherstrasse 74, 01307, Dresden, Germany

    Melinda Wuest, Birgit Eichhorn & Ursula Ravens

  2. APOGEPHA Arzneimittel GmbH, Kyffhäuser Strasse 27, 01309, Dresden, Germany

    Manfred Braeter & Gerhard Strugala

  3. Department of Pharmacology & Pharmacotherapy, AMC, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    Martin C. Michel

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  1. Melinda Wuest
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  2. Birgit Eichhorn
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Correspondence to Melinda Wuest.

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Wuest, M., Eichhorn, B., Braeter, M. et al. Muscarinic receptor expression and receptor-mediated detrusor contraction: comparison of juvenile and adult porcine tissue. Pflugers Arch - Eur J Physiol 456, 349–358 (2008). https://doi.org/10.1007/s00424-007-0407-z

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  • DOI: https://doi.org/10.1007/s00424-007-0407-z

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