Simonneaux V, Kienlen-Campard P, Loeffler J P, Basille M, Gonzalez B J, Vaudry H, Robberecht P, Pévet P
Laboratoire de Neurobiologie des Fonctions Rythmiques et Saisonnières, URA-CNRS 1332, Université Louis Pasteur, Strasbourg, France.
Neuroscience. 1998 Aug;85(3):887-96. doi: 10.1016/s0306-4522(97)00668-4.
Melatonin secretion from the mammalian pineal gland is strongly stimulated by noradrenaline and also by vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Three types of receptors for VIP and PACAP have been characterized so far: VIP1/PACAP receptors and VIP2/PACAP receptors, which possess similar high affinities for VIP and PACAP, and PACAP1 receptors which exhibit a 100-1000-fold higher affinity for PACAP. The aim of the present study was to characterize the receptor subtype(s) mediating the stimulatory effects of VIP and PACAP on melatonin synthesis in the rat pineal gland. Autoradiographic studies showed that PACAP and VIP were equally potent in displacing binding of radioiodinated PACAP27 from pineal sections. Amplification of pineal complementary DNAs by polymerase chain reaction using specific primers for the different receptor subtypes revealed that all three receptor messenger RNAs are expressed and that VIP1/PACAP receptor messenger RNA was predominant over VIP2/PACAP receptor messenger RNA. In vitro, VIP and PACAP stimulated melatonin synthesis with similar high potency and the effect of the two peptides were not additive. The selective VIP1/PACAP receptor agonists [R16]chicken secretin (1-25) and [K15, R16, L27]VIP(1-7)/growth hormone releasing factor(8-27) were significantly more potent than the selective VIP2/PACAP receptor agonist RO 25-1553 in stimulating melatonin secretion. The stimulatory effects of VIP and PACAP were similarly inhibited by the VIP1/PACAP antagonist [acetyl-His1, D-Phe2, K15, R16, L27]VIP(3-7)/growth hormone releasing factor(8-27). These data strongly suggest that VIP and PACAP exert a stimulatory effect on melatonin synthesis mainly through activation of a pineal VIP1/PACAP receptor subtype.
去甲肾上腺素以及血管活性肠肽（VIP）和垂体腺苷酸环化酶激活肽（PACAP）能强烈刺激哺乳动物松果体分泌褪黑素。目前已鉴定出三种VIP和PACAP受体：VIP1/PACAP受体和VIP2/PACAP受体，它们对VIP和PACAP具有相似的高亲和力，以及对PACAP表现出高100 - 1000倍亲和力的PACAP1受体。本研究的目的是鉴定介导VIP和PACAP对大鼠松果体褪黑素合成刺激作用的受体亚型。放射自显影研究表明，PACAP和VIP在取代松果体切片中放射性碘化PACAP27的结合方面同样有效。使用针对不同受体亚型的特异性引物通过聚合酶链反应扩增松果体互补DNA，结果显示所有三种受体信使RNA均有表达，且VIP1/PACAP受体信使RNA比VIP2/PACAP受体信使RNA占优势。在体外，VIP和PACAP以相似的高效能刺激褪黑素合成，且两种肽的作用无相加性。选择性VIP1/PACAP受体激动剂[R16]鸡促胰液素（1 - 25）和[K15，R16，L27]VIP(1 - 7)/生长激素释放因子(8 - 27)在刺激褪黑素分泌方面比选择性VIP2/PACAP受体激动剂RO 25 - 1553显著更有效。VIP和PACAP的刺激作用同样被VIP1/PACAP拮抗剂[乙酰 - His1，D - Phe2，K15，R16，L27]VIP(3 - 7)/生长激素释放因子(8 - 27)抑制。这些数据强烈表明，VIP和PACAP主要通过激活松果体VIP1/PACAP受体亚型对褪黑素合成发挥刺激作用。
