Kerr Karen P
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Jun;373(3):237-44. doi: 10.1007/s00210-006-0061-6. Epub 2006 Apr 28.
The aim of this study was to investigate the effect of histamine on field-stimulated contractions of the guinea-pig prostate using isolated preparations in organ bath experiments. The histamine receptor subtype involved in potentiating the twitch responses was characterised, and the presence of any post-synaptic effects was determined. In addition, the effects of histamine on nerve-stimulated contractions of the ventral and dorsal prostate as well as the coagulating gland were compared in preliminary experiments. Histamine (300 microM) approximately doubled the magnitude of the twitch contractions in the ventral and dorsal lobes of the prostate (nerve stimulation parameters were 10 Hz for 2 s every 50 s, 0.5 ms duration at supramaximal voltage). In the coagulating glands, histamine increased the contractions more than fourfold. Further experiments were performed only on the ventral glands. The H(1) receptor antagonist, mepyramine, exhibited an apparent competitive antagonism against the histamine-induced potentiations of the twitch responses (apparent pK(B) value = 9.21+/-0.17 (n=5). The H(2) receptor antagonist, ranitidine, produced a small, significant shift to the right, as did the time control. The H(3) receptor antagonist, thioperamide, had no significant effect on the concentration-response curve. The effects of histamine (10 microM) on exogenously applied acetylcholine (Ach), noradrenaline (NA) and adenosine 5'-triphosphate (ATP) were determined. In each case, the contractile responses were significantly potentiated: ATP (5.8-fold P<0.0001, n=8), NA (1.6-fold P<0.05, n=10) and Ach (2.1-fold P<0.0007, n=10). This is the first study that has shown the effects of histamine on field-stimulated contractions in the prostate of any species. It is concluded that histamine, acting on H(1) receptors, elicits a considerable potentiation of the nerve-stimulated twitch contractions in the guinea-pig prostate. One mechanism whereby histamine exerts its potentiating effect is a post-synaptic enhancement of the response to ATP in particular, but also to NA and Ach. It is suggested that H(1)-receptor and purinoceptor antagonists may have a role to play in the treatment of benign prostatic hyperplasia (BPH).
本研究的目的是在器官浴实验中使用离体标本，研究组胺对豚鼠前列腺场刺激收缩的影响。对参与增强抽搐反应的组胺受体亚型进行了表征，并确定了是否存在任何突触后效应。此外，在初步实验中比较了组胺对腹侧和背侧前列腺以及凝固腺神经刺激收缩的影响。组胺（300微摩尔）使前列腺腹侧和背侧叶的抽搐收缩幅度增加了约一倍（神经刺激参数为每50秒10赫兹持续2秒，在超最大电压下持续时间为0.5毫秒）。在凝固腺中，组胺使收缩增加了四倍多。进一步的实验仅在腹侧腺体上进行。H(1)受体拮抗剂美吡拉敏对组胺诱导的抽搐反应增强表现出明显的竞争性拮抗作用（表观pK(B)值 = 9.21±0.17，n = 5）。H(2)受体拮抗剂雷尼替丁使曲线有一个小的、显著的右移，时间对照也是如此。H(3)受体拮抗剂硫代哌酰胺对浓度 - 反应曲线没有显著影响。测定了组胺（10微摩尔）对外源性应用的乙酰胆碱（Ach）、去甲肾上腺素（NA）和腺苷5'-三磷酸（ATP）的影响。在每种情况下，收缩反应均显著增强：ATP（5.8倍，P < 0.0001，n = 8）、NA（1.6倍，P < 0.05，n = 10）和Ach（2.1倍，P < 0.0007，n = 10）。这是第一项表明组胺对任何物种前列腺场刺激收缩有影响的研究。得出的结论是，组胺作用于H(1)受体，可引起豚鼠前列腺神经刺激抽搐收缩的显著增强。组胺发挥其增强作用的一种机制特别是突触后对ATP反应的增强，对NA和Ach的反应也增强。有人提出H(1)受体和嘌呤受体拮抗剂可能在良性前列腺增生（BPH）的治疗中发挥作用。
