Abstract：
Phospholipases A2 (PLA2 ) may be involved in α1 -adrenergic contraction by formation of thromboxane A2 in different smooth muscle types. However, whether this mechanism occurs with α1 -adrenergic contractions of the prostate, is still unknown. While α1 -adrenoceptor antagonists are the first line option for medical treatment of voiding symptoms in benign prostatic hyperplasia (BPH), improvements are limited, probably by nonadrenergic contractions including thromboxane A2 . Here, we examined effects of PLA2 inhibitors on contractions of human prostate tissues.
Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS) and by α1 -adrenergic agonists in an organ bath, after application of the cytosolic PLA2 inhibitors ASB14780 and AACOCF3, the secretory PLA2 inhibitor YM26734, the leukotriene receptor antagonist montelukast, or of solvent to controls.
Frequency-dependent contractions of human prostate tissues induced by EFS were inhibited by 25% at 8 Hz, 38% at 16 Hz and 37% at 32 Hz by ASB14780 (1 µM), and by 32% at 16 Hz and 22% at 32 Hz by AACOCF3 (10 µM). None of both inhibitors affected contractions induced by noradrenaline, phenylephrine or methoxamine. YM26734 (3 µM) and montelukast (0.3 and 1 µM) neither affected EFS-induced contractions, nor contractions by α1 -adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM).
Our findings suggest presynaptic PLA2 functions in prostate smooth muscle contraction, while contractions induced by α1 -adrenergic agonists occur PLA2 -independent. Lacking sensitivity to montelukast excludes an involvement of PLA2 -derived leukotrienes in promotion of contractile neurotransmission.
Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS) and by α1 -adrenergic agonists in an organ bath, after application of the cytosolic PLA2 inhibitors ASB14780 and AACOCF3, the secretory PLA2 inhibitor YM26734, the leukotriene receptor antagonist montelukast, or of solvent to controls.
Frequency-dependent contractions of human prostate tissues induced by EFS were inhibited by 25% at 8 Hz, 38% at 16 Hz and 37% at 32 Hz by ASB14780 (1 µM), and by 32% at 16 Hz and 22% at 32 Hz by AACOCF3 (10 µM). None of both inhibitors affected contractions induced by noradrenaline, phenylephrine or methoxamine. YM26734 (3 µM) and montelukast (0.3 and 1 µM) neither affected EFS-induced contractions, nor contractions by α1 -adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM).
Our findings suggest presynaptic PLA2 functions in prostate smooth muscle contraction, while contractions induced by α1 -adrenergic agonists occur PLA2 -independent. Lacking sensitivity to montelukast excludes an involvement of PLA2 -derived leukotrienes in promotion of contractile neurotransmission.
摘要：
背景：磷脂酶A2（PLA2）可能通过在不同类型的平滑肌中形成血栓烷A2而参与α1-肾上腺素能收缩。然而,这种机制是否与前列腺的α1-肾上腺素能收缩发生，仍然未知。虽然α1-肾上腺素受体拮抗剂是良性前列腺增生（BPH）的排尿症状的药物治疗的一线选择，改进是有限的，可能是非肾上腺素能收缩，包括血栓烷A2。这里,我们研究了PLA2抑制剂对人前列腺组织收缩的影响.
方法：从根治性前列腺切除术中获得前列腺组织。在器官浴中通过电场刺激（EFS）和α1-肾上腺素能激动剂诱导收缩，在应用细胞溶质PLA2抑制剂ASB14780和AACOCF3，分泌性PLA2抑制剂YM26734，白三烯受体拮抗剂孟鲁司特后，或溶剂对控制。
结果：由EFS引起的人前列腺组织的频率依赖性收缩在8Hz时被抑制了25％，ASB14780（1µM）在16Hz时为38％，在32Hz时为37％，AACOCF3（10µM）在16Hz时下降32％，在32Hz时下降22％。两种抑制剂均不影响去甲肾上腺素诱导的收缩，去氧肾上腺素或甲氧胺。YM26734（3µM）和孟鲁司特（0.3和1µM）均不影响EFS诱导的收缩，α1-肾上腺素能激动剂也没有收缩，而所有的收缩被西洛多辛（100nM）基本上抑制。
结论：我们的研究结果表明，突触前PLA2在前列腺平滑肌收缩中的功能，而α1-肾上腺素能激动剂诱导的收缩发生不依赖PLA2的。对孟鲁司特缺乏敏感性排除了PLA2衍生的白三烯在促进收缩性神经传递中的参与。
方法：从根治性前列腺切除术中获得前列腺组织。在器官浴中通过电场刺激（EFS）和α1-肾上腺素能激动剂诱导收缩，在应用细胞溶质PLA2抑制剂ASB14780和AACOCF3，分泌性PLA2抑制剂YM26734，白三烯受体拮抗剂孟鲁司特后，或溶剂对控制。
结果：由EFS引起的人前列腺组织的频率依赖性收缩在8Hz时被抑制了25％，ASB14780（1µM）在16Hz时为38％，在32Hz时为37％，AACOCF3（10µM）在16Hz时下降32％，在32Hz时下降22％。两种抑制剂均不影响去甲肾上腺素诱导的收缩，去氧肾上腺素或甲氧胺。YM26734（3µM）和孟鲁司特（0.3和1µM）均不影响EFS诱导的收缩，α1-肾上腺素能激动剂也没有收缩，而所有的收缩被西洛多辛（100nM）基本上抑制。
结论：我们的研究结果表明，突触前PLA2在前列腺平滑肌收缩中的功能，而α1-肾上腺素能激动剂诱导的收缩发生不依赖PLA2的。对孟鲁司特缺乏敏感性排除了PLA2衍生的白三烯在促进收缩性神经传递中的参与。
