Barrett Perry, Messager Sophie, Schuster Carole, Moar Kim M, Mercer Julian G, Morgan Peter J
Rowett Research Institute and Aberdeen Center for Energy Regulation and Obesity, Bucksburn, Aberdeen, United Kingdom AB21 9SB.
Endocrinology. 2002 Jun;143(6):2366-75. doi: 10.1210/endo.143.6.8833.
The pars tuberalis (PT) region of the anterior pituitary plays a physiological role in seasonal animals. The primary signal transduction mechanism of the melatonin receptor in this tissue is an inhibition of cAMP signaling. However, nothing is known about the endocrine signals that activate cAMP synthesis in the cells of the PT, as previous studies relied on the pharmacological tool, forskolin, to stimulate cAMP synthesis. Here we show that pituitary adenylate cyclase-activating polypeptide (PACAP) activates cAMP synthesis in the cells of the PT. The pharmacology of cAMP activation by PACAP peptides suggests that cAMP activation is mediated by the type I PACAP receptor. PACAP treatment of PT cells results in cellular responses that are consistent with cAMP activation in these cells, including activation of MAPK and elevation of melatonin receptor mt1 mRNA expression. These responses can be inhibited by melatonin, demonstrating that activation of cAMP occurs within the melatonin-responsive cells. However, although PACAP activates cAMP in the cells of the PT, the effect of PACAP may not be direct, as colocalization in situ hybridization studies demonstrates that the type I PACAP receptor and the melatonin mt1 receptor do not colocalize on the cells of the PT.
垂体前叶的结节部（PT）在季节性动物中发挥着生理作用。该组织中褪黑素受体的主要信号转导机制是抑制cAMP信号传导。然而，关于激活PT细胞中cAMP合成的内分泌信号却一无所知，因为先前的研究依赖于药理学工具福司可林来刺激cAMP合成。在此我们表明，垂体腺苷酸环化酶激活多肽（PACAP）可激活PT细胞中的cAMP合成。PACAP肽激活cAMP的药理学表明，cAMP激活是由I型PACAP受体介导的。用PACAP处理PT细胞会导致细胞反应，这些反应与这些细胞中的cAMP激活一致，包括MAPK的激活和褪黑素受体mt1 mRNA表达的升高。这些反应可被褪黑素抑制，表明cAMP的激活发生在褪黑素反应性细胞内。然而，尽管PACAP可激活PT细胞中的cAMP，但PACAP的作用可能不是直接的，因为原位杂交共定位研究表明，I型PACAP受体和褪黑素mt1受体在PT细胞上并不共定位。
