Kaji H, Chihara K, Abe H, Kita T, Kashio Y, Okimura Y, Fujita T
Endocrinology. 1985 Nov;117(5):1914-9. doi: 10.1210/endo-117-5-1914.
The present study was aimed to clarify, by use of the passive immunization method, the involvement of endogenous vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine amide (PHI)-like peptides in the stimulation of PRL-like immunoreactive material release induced by 5-hydroxy-L-tryptophan (5HTP), a serotonin precursor. We used conscious, freely moving male rats of the Wistar strain (BW, 250-300 g) chronically cannulated with atrial catheters. Anti-VIP serum (AVS) and anti-PHI serum (APS), each generated in rabbits against synthetic porcine VIP and natural porcine PHI, respectively, were highly potent [maximum binding capacity (Bmax): AVS, 55.5 nmol/ml; APS, 5.53 nmol/ml] and specific. Bolus injection of 5HTP (10 mg/kg BW) through the catheter caused a significant increase in plasma PRL (nanograms per ml) in rats pretreated with normal rabbit serum (NRS) [14.3 +/- (SE) 3.8----56.3 +/- 11.2], with AVS (12.3 +/- 3.5----48.5 +/- 6.2), with APS (10.5 +/- 3.9----43.5 +/- 8.8), and with AVS plus APS (9.0 +/- 1.4----28.5 +/- 2.7). The basal PRL concentrations did not differ significantly among these groups, whereas the PRL responses to 5HTP were significantly blunted in AVS plus APS-pretreated rats (P less than 0.05 vs. NRS). To eliminate the modification by dopaminergic control of 5HTP-induced PRL release, the next experiment was performed in rats repeatedly injected with sulpiride, a dopamine receptor antagonist (5 mg/kg BW), every 30 min. The first injection of sulpiride caused a prompt and marked increase in plasma PRL, followed by decreasing but still high levels of plasma PRL upon the subsequent injections of sulpiride every 30 min. The cumulative release area of PRL after pretreatment with AVS plus APS or APS alone was significantly lower than that after NRS (P less than 0.05). The same dose of 5HTP resulted in a significant further increase in plasma PRL exceeding the levels elevated by sulpiride injections in NRS-treated rats. Prior simultaneous administration of AVS and APS resulted in a complete suppression of 5HTP-induced PRL release, whereas pretreatment with either AVS or APS showed only a minimal effect. These results suggest that endogenous VIP and PHI-like peptides are PRL-releasing factors, involved at least in the mechanism of 5HTP-induced PRL release, in which the dopaminergic control may be also involved.
本研究旨在通过被动免疫法阐明内源性血管活性肠肽（VIP）和肽组氨酸异亮氨酸酰胺（PHI）样肽在5-羟色胺前体5-羟色氨酸（5HTP）诱导的催乳素样免疫反应性物质释放刺激中的作用。我们使用经心房插管的清醒、自由活动的Wistar品系雄性大鼠（体重250 - 300克）。分别针对合成猪VIP和天然猪PHI在兔体内产生的抗VIP血清（AVS）和抗PHI血清（APS）具有高效能[最大结合容量（Bmax）：AVS为55.5 nmol/ml；APS为5.53 nmol/ml]且具有特异性。通过导管推注5HTP（10 mg/kg体重）导致用正常兔血清（NRS）预处理的大鼠[14.3 ±（标准误）3.8 ---- 56.3 ± 11.2]、用AVS预处理的大鼠（12.3 ± 3.5 ---- 48.5 ± 6.2）、用APS预处理的大鼠（10.5 ± 3.9 ---- 43.5 ± 8.8）以及用AVS加APS预处理的大鼠（9.0 ± 1.4 ---- 28.5 ± 2.7）的血浆催乳素（每毫升纳克数）显著增加。这些组之间的基础催乳素浓度无显著差异，而在AVS加APS预处理的大鼠中，对5HTP的催乳素反应显著减弱（与NRS相比，P < 0.05）。为消除多巴胺能对5HTP诱导的催乳素释放的调节作用，在每30分钟重复注射多巴胺受体拮抗剂舒必利（5 mg/kg体重）的大鼠中进行了下一个实验。首次注射舒必利导致血浆催乳素迅速且显著增加，随后每30分钟注射舒必利后血浆催乳素水平虽有所下降但仍维持在较高水平。用AVS加APS或单独用APS预处理后催乳素的累积释放面积显著低于用NRS预处理后的累积释放面积（P < 0.05）。相同剂量的5HTP导致血浆催乳素进一步显著增加，超过了NRS处理大鼠中舒必利注射所升高的水平。预先同时给予AVS和APS可完全抑制5HTP诱导的催乳素释放，而单独用AVS或APS预处理仅显示出最小的作用。这些结果表明内源性VIP和PHI样肽是催乳素释放因子，至少参与了5HTP诱导的催乳素释放机制，其中多巴胺能调节可能也参与其中。
