Simonneaux V, Kozak R, Arsenijévic Y, Pévet P
URA-CNRS 1332, Université Louis Pasteur, Strasbourg, France.
Regul Pept. 1996 Jan 16;61(1):63-9. doi: 10.1016/0167-0115(95)00139-5.
The pineal gland releases the "time-keeping' hormone melatonin following a rhythmic sympathetic input which translates light information. The aim of this work was to study the role and mechanism of action of the central vasopressinergic input on pineal cAMP-dependent melatonin synthesis in the rat. The pineal was found to display vasopressin receptors of the V1a subtype, as the V1a antagonist [125I]HO-LVA bound in a saturable manner to pineal membranes with a high affinity (kd = 10 pM) and a maximal binding capacity (B(max)) of 13 fmol/mg protein. Vasopressin was able to displace [125I]HO-LVA binding in a dose-dependent manner (k(i) = 1.9 nM). Vasopressin had no effect on the basal cAMP level and melatonin secretion in cultured rat pinealocytes. However, it clearly and dose-dependently (EC50 = 7 nM) potentiated by 2-3 times cAMP accumulation and by 1.5-2.5 times melatonin secretion induced by moderate noradrenergic stimulation. On strongly stimulated pinealocytes, however, vasopressin could potentiate cAMP accumulation, but not melatonin secretion. The potentiatory effect of vasopressin was inhibited in the presence of the V1a antagonist. These results indicate that vasopressin is a potent modulator of rat pineal synthetic activity.
松果体在节律性交感神经输入后释放“计时”激素褪黑素，该交感神经输入可转化光信息。这项工作的目的是研究中枢血管加压素能输入对大鼠松果体中依赖环磷酸腺苷（cAMP）的褪黑素合成的作用及作用机制。研究发现松果体表达V1a亚型的血管加压素受体，因为V1a拮抗剂[125I]HO-LVA以饱和方式与松果体膜结合，亲和力高（解离常数kd = 10 pM），最大结合容量（B(max)）为13 fmol/mg蛋白质。血管加压素能够以剂量依赖方式取代[125I]HO-LVA的结合（抑制常数k(i) = 1.9 nM）。血管加压素对培养的大鼠松果体细胞的基础cAMP水平和褪黑素分泌没有影响。然而，它能明显且呈剂量依赖性地（半数有效浓度EC50 = 7 nM）使中等程度去甲肾上腺素能刺激诱导的cAMP积累增加2 - 3倍，褪黑素分泌增加1.5 - 2.5倍。然而，在强烈刺激的松果体细胞中，血管加压素能增强cAMP积累，但不能增强褪黑素分泌。在V1a拮抗剂存在的情况下，血管加压素的增强作用受到抑制。这些结果表明血管加压素是大鼠松果体合成活性的有效调节剂。
