Gray Katherine T, Short Jennifer L, Ledent Catherine, Ventura Sab
Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Eur J Pharmacol. 2008 Sep 11;592(1-3):151-7. doi: 10.1016/j.ejphar.2008.07.003. Epub 2008 Jul 10.
Prostatic A2A adenosine receptors mediate varied effects. This study aimed to test whether genetic disruption of this receptor affects prostate contractility. Prostates taken from mice which were homozygous (A2AR-/-) and heterozygous (A2AR+/-) for the disrupted A2A adenosine receptor gene and wild-type littermates (A2AR +/+) were mounted in organ baths. Contractile responses to nerve stimulation and noradrenaline were measured in the presence of various pharmacological tools. Electrical field stimulation (0.5 ms pulse duration, 60 V, 0.1-20 Hz) yielded frequency-dependent contractions while exogenous administration of noradrenaline (10 nM-1 mM) or tyramine (1 microM-1 mM) produced concentration-dependent responses. Contractile responses to electrical field stimulation from A2AR-/- and A2AR+/- prostates were reduced when compared to A2A+/+ prostates (P=0.013, n=33-36). Prazosin (0.3 microM) inhibited electrical field stimulation-induced responses in prostates from A2AR+/+ and A2AR+/- mice (P< or =0.016, n=5-7) but not A2AR-/- mice (P=0.400, n=6). Tetrodotoxin abolished electrical field stimulation-induced responses in all prostates (P<0.001, n=5-7). NF 449 and ZM 241385 were without effect (P< or =0.421, n=4-6). There were no genotype differences in noradrenaline or tyramine concentration-response curves (P> or =0.180, n=10-13). Prazosin (0.3 microM) and cocaine (10 microM) attenuated the responses induced by noradrenaline (P<0.001, n=6-7) and tyramine (P<0.001, n=5-6), respectively, in all genotypes. Disruption of the A2A adenosine receptor leads to reduced nerve mediated contractile responses of the prostate in mature mice.
前列腺A2A腺苷受体介导多种效应。本研究旨在测试该受体的基因破坏是否会影响前列腺的收缩性。将取自纯合子（A2AR-/-）和杂合子（A2AR+/-）A2A腺苷受体基因破坏小鼠以及野生型同窝小鼠（A2AR +/+）的前列腺置于器官浴槽中。在存在各种药理学工具的情况下，测量对神经刺激和去甲肾上腺素的收缩反应。电场刺激（脉冲持续时间0.5毫秒，60伏，0.1 - 20赫兹）产生频率依赖性收缩，而外源性给予去甲肾上腺素（10纳摩尔 - 1毫摩尔）或酪胺（1微摩尔 - 1毫摩尔）产生浓度依赖性反应。与A2A+/+前列腺相比，A2AR-/-和A2AR+/-前列腺对电场刺激的收缩反应降低（P = 0.013，n = 33 - 36）。哌唑嗪（0.3微摩尔）抑制A2AR+/+和A2AR+/-小鼠前列腺中电场刺激诱导的反应（P≤0.016，n = 5 - 7），但不抑制A2AR-/-小鼠的反应（P = 0.400，n = 6）。河豚毒素消除了所有前列腺中电场刺激诱导的反应（P<0.001，n = 5 - 7）。NF 449和ZM 241385无效（P≤0.421，n = 4 - 6）。去甲肾上腺素或酪胺浓度 - 反应曲线无基因型差异（P≥0.180，n = 10 - 13）。哌唑嗪（0.3微摩尔）和可卡因（10微摩尔）分别减弱了所有基因型中去甲肾上腺素（P<0.001，n = 6 - 7）和酪胺（P<0.001，n = 5 - 6）诱导的反应。A2A腺苷受体的破坏导致成熟小鼠前列腺神经介导的收缩反应降低。
