The alpha1A-adrenoceptor gene is required for the alpha1L-adrenoceptor-mediated response in isolated preparations of the mouse prostate.
OBJECTIVE
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.


METHODS
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.


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
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.
Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
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D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D010641:Phenotype; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C547714:Adra1a protein, mouse; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine; D011224:Prazosin