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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ventura, S. Gray, Kt Short, Jl |
| Description | Author Affiliation: Gray K ( Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.) |
| Abstract | BACKGROUND AND PURPOSE: This study investigated whether deletion of the alpha1A-adrenoceptor gene influences contractile responses of mouse prostate to noradrenaline. Responses of mouse prostate to noradrenaline are known to be mediated by alpha1L-adrenoceptors, which are thought to be a functional phenotype of alpha1A-adrenoceptor. EXPERIMENTAL APPROACH: Prostate tissues from alpha1A-adrenoceptor knockout mice which were homozygous (alpha1A -/-) and heterozygous (alpha1A +/-) for the disrupted alpha1A-adrenoceptor gene, as well as wild-type (alpha1A +/+) 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 alpha1A-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 alpha1A -/- mice elicited an approximately 30% decreased response compared with prostates from alpha(1A)+/+ mice. Prazosin (0.3 muM) attenuated responses to electrical field stimulation in prostates from alpha1A +/+ and alpha1A +/- mice but not from alpha1A -/- mice. Increasing concentrations of exogenously administered noradrenaline (10 nM-1 mM) produced mean concentration-response curves in prostates from alpha1A +/+ and alpha1A +/- mice, which were not different. Maximum responses to noradrenaline were decreased by approximately 80% in prostates from alpha1A -/- mice compared with alpha1A +/+ mice. Prazosin attenuated responses to noradrenaline in all genotypes. CONCLUSIONS AND IMPLICATIONS: alpha1L-Adrenoceptor-mediated responses in mouse prostate are abolished in alpha1A -/- mice, demonstrating that the alpha1A-adrenoceptor gene is essential to the manifestation of the prostatic alpha1L-adrenoceptor phenotype. This implies that alpha1L-adrenoceptors are indeed a functional phenotype of alpha1A-adrenoceptor. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 155 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2008-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Muscle Contraction Norepinephrine Metabolism Prostate Receptors, Adrenergic, Alpha-1 Adrenergic Alpha-1 Receptor Antagonists Adrenergic Alpha-Antagonists Pharmacology Animals Electric Stimulation Genotype Mice Mice, Inbred C57BL Mice, Knockout Drug Effects Phenotype Prazosin Deficiency Genetics Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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