The α1A-adrenoceptor gene is required for the α1L-adrenoceptor-mediated response in isolated preparations of the mouse prostate

Authors

  • K T Gray,

    1. Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
    Search for more papers by this author
  • J L Short,

    1. Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
    Search for more papers by this author
  • S Ventura

    Corresponding author
    1. Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
    Search for more papers by this author

Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia. E-mail: Sab.Ventura@vcp.monash.edu.au

Abstract

Background and purpose:

This study investigated whether deletion of the α1A-adrenoceptor gene influences contractile responses of mouse prostate to noradrenaline. Responses of mouse prostate to noradrenaline are known to be mediated by α1L-adrenoceptors, which are thought to be a functional phenotype of α1A-adrenoceptor.

Experimental approach:

Prostate tissues from α1A-adrenoceptor knockout mice which were homozygous (α1A−/−) and heterozygous (α1A+/−) for the disrupted α1A-adrenoceptor gene, as well as wild-type (α1A+/+) littermates were mounted in glass-isolated organ baths. Electrical field stimulation of nerves and exogenous application of noradrenaline were used to investigate the effects of α1A-adrenoceptor disruption on prostate contractility.

Key results:

Frequency–response curves to electrical field stimulation (0.5 ms pulse duration, 60 V, 0.1–20 Hz) yielded frequency-dependent contractions. At frequencies of 10 and 20 Hz, prostates from α1A−/− mice elicited an approximately 30% decreased response compared with prostates from α1A+/+ mice. Prazosin (0.3 μM) attenuated responses to electrical field stimulation in prostates from α1A+/+ and α1A+/− mice but not from α1A−/− mice. Increasing concentrations of exogenously administered noradrenaline (10 nM–1 mM) produced mean concentration–response curves in prostates from α1A+/+ and α1A+/− mice, which were not different. Maximum responses to noradrenaline were decreased by approximately 80% in prostates from α1A−/− mice compared with α1A+/+ mice. Prazosin attenuated responses to noradrenaline in all genotypes.

Conclusions and implications:

α1L-Adrenoceptor-mediated responses in mouse prostate are abolished in α1A−/− mice, demonstrating that the α1A-adrenoceptor gene is essential to the manifestation of the prostatic α1L-adrenoceptor phenotype. This implies that α1L-adrenoceptors are indeed a functional phenotype of α1A-adrenoceptor.

British Journal of Pharmacology (2008) 155, 103–109; doi:fn1; published online 16 June 2008

Ancillary