Lutz T A, Tschudy S, Rushing P A, Scharrer E
Institute of Veterinary Physiology, University of Zürich, Winterthurerstrasse 260, 8057, Zürich, Switzerland.
Peptides. 2000 Feb;21(2):233-8. doi: 10.1016/s0196-9781(99)00208-9.
The teleost salmon calcitonin (sCT), but not mammalian CT, shows similar biologic actions in the skeletal muscle as amylin and calcitonin gene-related peptide (CGRP). The peptides have also been shown to reduce food intake in rams. Because sCT, but not amylin, binds irreversibly to amylin binding sites, the aim of the present study was to compare the anorectic potency of both peptides. To determine whether sCT reduces food intake through interaction with amylin binding sites, we also tested whether appropriate antagonists (CORP 8-37, AC 187) attenuate the anorectic effect of sCT. Finally, we wanted to know whether rat calcitonin (rCT) and sCT reduce food intake to the same extent. Peptides were injected intraperitoneally at dark onset in 24 h food-deprived rats. At doses of 5 or 0.5 microg/kg, the anorectic effect of sCT was more potent and lasted much longer (e.g. 5 microg/kg: sCT > 10 h; amylin approx. 2 h) than that of amylin. Both CORP 8-37 and AC 187 (10 microg/kg) markedly reduced the anorectic action of sCT (0.5 microg/kg). In contrast to sCT, rCT (0.5 microg/kg) had no effect on food intake. It is concluded that sCT s anorectic effect is partly mediated by amylin receptors. Irreversible binding of sCT to amylin receptors may lead to a stronger and prolonged effect in comparison to amylin due to a sustained activation of the binding sites. Similar to other actions of CTs, the anorectic potency of sCT in rats was higher than that of mammalian (rat) CT. This agrees with binding profiles of amylin, sCT, and rCT at amylin binding sites as observed in in vitro studies.
硬骨鱼降钙素（sCT）而非哺乳动物降钙素（CT），在骨骼肌中显示出与胰淀素和降钙素基因相关肽（CGRP）相似的生物学作用。这些肽也已被证明可减少公羊的食物摄入量。由于sCT而非胰淀素不可逆地结合到胰淀素结合位点，本研究的目的是比较这两种肽的食欲抑制效力。为了确定sCT是否通过与胰淀素结合位点相互作用来减少食物摄入量，我们还测试了合适的拮抗剂（CORP 8 - 37、AC 187）是否会减弱sCT的食欲抑制作用。最后，我们想知道大鼠降钙素（rCT）和sCT减少食物摄入量的程度是否相同。在禁食24小时的大鼠中，于黑暗开始时腹腔注射这些肽。在5或0.5微克/千克的剂量下，sCT的食欲抑制作用比胰淀素更强且持续时间更长（例如，5微克/千克：sCT > 10小时；胰淀素约2小时）。CORP 8 - 37和AC 187（10微克/千克）均显著降低了sCT（0.5微克/千克）的食欲抑制作用。与sCT相反，rCT（0.5微克/千克）对食物摄入量没有影响。得出的结论是，sCT的食欲抑制作用部分由胰淀素受体介导。与胰淀素相比，sCT与胰淀素受体的不可逆结合可能由于结合位点的持续激活而导致更强且更持久的作用。与CT的其他作用类似，sCT在大鼠中的食欲抑制效力高于哺乳动物（大鼠）CT。这与体外研究中观察到的胰淀素、sCT和rCT在胰淀素结合位点的结合情况相符。
