Juarranz M G, De Neef P, Robberecht P
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Brussels, Belgium.
Prostate. 1999 Sep 15;41(1):1-6. doi: 10.1002/(sici)1097-0045(19990915)41:1<1::aid-pros1>3.0.co;2-a.
The 28-amino-acid neuropeptide vasoactive intestinal peptide (VIP) might play an important role in the physiology of the prostate, since it stimulates glandular secretion, inhibits muscle contraction, stimulates proliferation of epithelial cells, and increases the secretion of prostate-specific antigen (PSA). This neuropeptide may act through interaction with two types of high-affinity receptors, named VPAC(1) and VPAC(2) receptors. Recently, selective agonists and antagonists for each receptor subtype were synthesized. We used them to identify the VIP receptor subclass expressed in rat prostatic tissue.
We tested the capacity of selective labeled and unlabeled agonists and antagonists of VPAC(1) and VPAC(2) receptors to bind to rat prostatic membranes and to stimulate or prevent the stimulation of adenylate cyclase activity.
The following selective peptides were used: VPAC(1) agonist ([K(15), R(16), L(27)] VIP (1-7)/GRF (8-27)); VPAC(1) antagonist (PG 97-269); and VPAC(2) agonist (RO 25-1553). The IC(50) values of [(125)I]-VIP binding inhibition for the different peptides in rat prostatic membranes were: VIP (1.7 nM) < VPAC(1) agonist (20 nM) < VPAC(1) antagonist (40 nM) < VPAC(2) agonist (329 nM). The EC(50) values of adenylate cyclase stimulation were similar to the IC(50) values for each peptide, and the Ki values for the VPAC(1) antagonist, inhibiting the adenylate cyclase activity stimulated by VIP and the VPAC(1) agonist, were 22 and 35 nM, respectively. Comparison of binding of [(125)I]-VIP and of [(125)I]-RO 25-1553 indicates the presence of 80% of VPAC(1) and 20% VPAC(2) receptors.
In rat prostate membranes, VPAC(1) receptors are largely predominant. Binding studies were compatible with a ratio of 80/20 of VPAC(1)/VPAC(2) receptors, whereas functionally only VPAC(1) receptors were detected.
28个氨基酸的神经肽血管活性肠肽（VIP）可能在前列腺生理过程中发挥重要作用，因为它能刺激腺体分泌、抑制肌肉收缩、刺激上皮细胞增殖并增加前列腺特异性抗原（PSA）的分泌。这种神经肽可能通过与两种高亲和力受体相互作用发挥作用，这两种受体分别称为VPAC(1)和VPAC(2)受体。最近，已合成了针对每种受体亚型的选择性激动剂和拮抗剂。我们使用它们来鉴定大鼠前列腺组织中表达的VIP受体亚类。
我们测试了VPAC(1)和VPAC(2)受体的选择性标记和未标记激动剂及拮抗剂与大鼠前列腺膜结合的能力，以及刺激或阻止腺苷酸环化酶活性刺激的能力。
使用了以下选择性肽：VPAC(1)激动剂（[K(15), R(16), L(27)] VIP (1 - 7)/GRF (8 - 27)）；VPAC(1)拮抗剂（PG 97 - 269）；以及VPAC(2)激动剂（RO 25 - 1553）。在大鼠前列腺膜中，不同肽对[(125)I]-VIP结合抑制的IC(50)值为：VIP（1.7 nM）< VPAC(1)激动剂（20 nM）< VPAC(1)拮抗剂（40 nM）< VPAC(2)激动剂（329 nM）。腺苷酸环化酶刺激的EC(50)值与每种肽的IC(50)值相似，抑制由VIP和VPAC(1)激动剂刺激的腺苷酸环化酶活性的VPAC(1)拮抗剂的Ki值分别为22 nM和35 nM。[(125)I]-VIP与[(125)I]-RO 25 - 1553结合的比较表明存在80%的VPAC(1)受体和20%的VPAC(2)受体。
在大鼠前列腺膜中，VPAC(1)受体占主导地位。结合研究与VPAC(1)/VPAC(2)受体80/20的比例相符，而在功能上仅检测到VPAC(1)受体。
