期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 155, 期 1, 页码 103-109出版社
WILEY
DOI: 10.1038/bjp.2008.245
关键词
noradrenaline; prazosin; tamsulosin; benign prostatic hyperplasia; BPH; smooth muscle; nerve stimulation
资金
- Appel Family Bequest
- Arthur and Mary Osborn Estate
- National Health & Medical Research Council (Australia)
Background and purpose: This study investigated whether deletion of the alpha(1A)-adrenoceptor gene influences contractile responses of mouse prostate to noradrenaline. Responses of mouse prostate to noradrenaline are known to be mediated by alpha(1L)-adrenoceptors, which are thought to be a functional phenotype of alpha(1A)-adrenoceptor. Experimental approach: Prostate tissues from alpha(1A)-adrenoceptor knockout mice which were homozygous (alpha(1A)-/-) and heterozygous (alpha(1A)+/-) for the disrupted alpha(1A)-adrenoceptor gene, as well as wild-type (alpha(1A)+/+) 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 alpha(1A)-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 alpha(1A)-/- mice elicited an approximately 30% decreased response compared with prostates from alpha(1A)+/+ mice. Prazosin (0.3 mM) attenuated responses to electrical field stimulation in prostates from alpha(1A)+/+ and alpha(1A)+/- mice but not from alpha(1A)-/- mice. Increasing concentrations of exogenously administered noradrenaline (10 nM-1mM) produced mean concentration-response curves in prostates from alpha(1A)+/+ and alpha(1A)+/- mice, which were not different. Maximum responses to noradrenaline were decreased by approximately 80% in prostates from alpha(1A)-/- mice compared with alpha(1A)+/+ mice. Prazosin attenuated responses to noradrenaline in all genotypes. Conclusions and implications: alpha(1L)-Adrenoceptor-mediated responses in mouse prostate are abolished in alpha(1A)-/- mice, demonstrating that the alpha(1A)-adrenoceptor gene is essential to the manifestation of the prostatic alpha(1L)-adrenoceptor phenotype. This implies that alpha(1L)-adrenoceptors are indeed a functional phenotype of alpha(1A)-adrenoceptor.
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