Kester Robert R, Mooppan Unni M, Gousse Angelo E, Alver James E, Gintautas Jonas, Gulmi Frederick A, Abadir Adel R, Kim Hong
Departments of Urology and Anesthesiology, Brookdale University Medical Center, Brooklyn, NY, USA.
J Urol. 2003 Sep;170(3):1032-8. doi: 10.1097/01.ju.0000080440.74266.b1.
Human prostate contains alpha-1 adrenergic, cholinergic and nonadrenergic noncholinergic neuroreceptors. Using agonistic and antagonistic agents at these neuroreceptors we studied the resultant contractile responses in isolated human prostate.
Human prostate tissue was obtained at prostatectomy for benign prostatic hyperplasia in 37 adult male patients. Tissues were suspended in tissue bath chambers connected to force displacement transducers. Specimens were subjected to agonist induced contractions, the first always being norepinephrine (NE). Specimens were pretreated with antagonist (adrenergic, cholinergic, nonadrenergic noncholinergic or none if control), followed by contraction with a second agonist (NE or other). Contractile tensions were recorded on a polygraph and then statistically analyzed.
The order of highest to lowest agonist induced tensile forces was NE, dopamine, acetylcholine, bethanechol, histamine and serotonin. Excitatory concentration EC(50) values were determined for each agonist tested. Significant differences were found between specific alpha-1 adrenergic receptor blockers (terazosin, prazosin and the experimental drug LY253352). In addition, many other agents antagonized the alpha-1 adrenergic receptor. Inhibitory concentration IC(50) values were obtained and the order of alpha-1 adrenergic antagonistic strengths from strongest to weakest was LY253352, prazosin, terazosin, ketanserin, SCH23390, diphenhydramine, DO710, dopamine, serotonin and histamine.
Human prostate neuroreceptors were determined to be alpha-1 adrenergic, dopaminergic, muscarinic cholinergic, 2A serotonergic and H1 histaminergic. Dopamine, serotonin, histamine and their antagonists blocked the adrenergic response, indicating possible receptor-receptor interaction. Further study of the pharmacology of human prostate would likely identify new drugs for treating patients with bladder outlet obstruction due to benign prostatic hyperplasia.
人类前列腺含有α-1肾上腺素能、胆碱能和非肾上腺素能非胆碱能神经受体。我们使用这些神经受体的激动剂和拮抗剂，研究了离体人类前列腺产生的收缩反应。
从37例成年男性良性前列腺增生患者的前列腺切除术中获取人类前列腺组织。将组织悬挂在连接到力位移传感器的组织浴槽中。标本先接受激动剂诱导的收缩，第一次总是去甲肾上腺素（NE）。标本先用拮抗剂（肾上腺素能、胆碱能、非肾上腺素能非胆碱能或对照组不使用）预处理，然后用第二种激动剂（NE或其他）进行收缩。收缩张力在多道记录仪上记录，然后进行统计分析。
激动剂诱导的最大张力顺序为NE、多巴胺、乙酰胆碱、氨甲酰甲胆碱、组胺和5-羟色胺。测定了每种测试激动剂的兴奋浓度EC(50)值。在特定的α-1肾上腺素能受体阻滞剂（特拉唑嗪、哌唑嗪和实验药物LY253352）之间发现了显著差异。此外，许多其他药物也能拮抗α-1肾上腺素能受体。获得了抑制浓度IC(50)值，α-1肾上腺素能拮抗强度从最强到最弱的顺序为LY253352、哌唑嗪、特拉唑嗪、酮色林、SCH23390、苯海拉明、DO710、多巴胺、5-羟色胺和组胺。
人类前列腺神经受体被确定为α-1肾上腺素能、多巴胺能、毒蕈碱胆碱能、5-羟色胺2A能和H1组胺能。多巴胺、5-羟色胺、组胺及其拮抗剂阻断了肾上腺素能反应，表明可能存在受体-受体相互作用。对人类前列腺药理学的进一步研究可能会发现治疗良性前列腺增生所致膀胱出口梗阻患者的新药。
