Pagani F, Netti C, Guidobono F, Lattuada N, Ticozzi C, Sibilia V
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Neuroendocrinology. 1998 Sep;68(3):220-8. doi: 10.1159/000054369.
In this study we examined the possible interplay of amylin (AMY) and salmon calcitonin (sCT) in the central control of growth hormone (GH) and prolactin (PRL) secretion in male rats. For this purpose we first compared effects of central intracerebroventricular (i.c.v.) admininstration of various doses of AMY (2.5-2,500 ng/rat) and sCT (2.2-220 ng/rat) on beta-endorphin (beta-END, 0.5 microg/rat)-induced GH and PRL secretion. AMY and sCT dose-dependently inhibited beta-END-induced GH secretion, whereas only sCT was able to inhibit beta-END-induced PRL secretion. To examine whether the GH inhibitory effect of AMY was due to the possible cross-reactivity of AMY and sCT on the same receptors in the CNS, we pretreated some rats with the AMY antagonist (AMY8-37, 2. 5 microg/rat, i.c.v.). AMY8-37 significantly enhanced the GH-stimulatory action of beta-END. AMY8-37, administered prior to AMY and sCT, significantly removed the inhibitory effect of both AMY and sCT on beta-END-induced GH release, suggesting that both peptides mediate their response on GH through a common receptor. In vitro competition binding studies on rat hypothalamic membranes have shown that both AMY and sCT compete with [125I]rAMY binding with half inhibition (IC50) values of 3.6 x 10(-11) and 1.6 x 10(-10) M, respectively. Binding of [125I]sCT was inhibited by sCT with an IC50 of 1.09 x 10(-10) M and to a lesser extent by AMY with an IC50 of 1. 3 x 10(-6) M. Thus it is possible that the two peptides recognize a common hypothalamic receptor but with different affinities (sCT > AMY). Overall these data indicate that AMY behaves as a mimic of sCT in the central control of GH secretion. The failure of AMY, at variance with sCT, to modify the PRL-releasing activity of beta-END indicates that different receptor subtypes for sCT are involved in the endocrine effects of sCT and only those mediating the modulatory action of GH respond to AMY.
在本研究中，我们检测了男性大鼠体内胰岛淀粉样多肽（AMY）和鲑鱼降钙素（sCT）在生长激素（GH）和催乳素（PRL）分泌的中枢控制中可能存在的相互作用。为此，我们首先比较了脑室内（i.c.v.）注射不同剂量的AMY（2.5 - 2500 ng/大鼠）和sCT（2.2 - 220 ng/大鼠）对β-内啡肽（β-END，0.5 μg/大鼠）诱导的GH和PRL分泌的影响。AMY和sCT均剂量依赖性地抑制β-END诱导的GH分泌，而只有sCT能够抑制β-END诱导的PRL分泌。为了检测AMY对GH的抑制作用是否是由于AMY和sCT在中枢神经系统中对相同受体可能存在交叉反应，我们用AMY拮抗剂（AMY8 - 37，2.5 μg/大鼠，i.c.v.）预处理了一些大鼠。AMY8 - 37显著增强了β-END对GH的刺激作用。在AMY和sCT之前注射AMY8 - 37，可显著消除AMY和sCT对β-END诱导的GH释放的抑制作用，这表明这两种肽通过共同受体介导它们对GH的反应。对大鼠下丘脑膜进行的体外竞争结合研究表明，AMY和sCT均与[125I]rAMY竞争结合，其半数抑制（IC50）值分别为3.6×10⁻¹¹和1.6×10⁻¹⁰ M。[125I]sCT的结合被sCT抑制，IC50为1.09×10⁻¹⁰ M，被AMY抑制的程度较小，IC50为1.3×10⁻⁶ M。因此，这两种肽可能识别共同的下丘脑受体，但亲和力不同（sCT > AMY）。总体而言，这些数据表明在GH分泌的中枢控制中，AMY表现为sCT的模拟物。与sCT不同，AMY未能改变β-END的PRL释放活性，这表明sCT的不同受体亚型参与了sCT的内分泌作用，并且只有那些介导GH调节作用的受体对AMY有反应。
