Morimoto T, Okamoto M, Koida M, Nakamuta H, Stahl G L, Orlowski R C
Jpn J Pharmacol. 1985 Jan;37(1):21-9. doi: 10.1254/jjp.37.21.
Intracerebroventricular (i.c.v.) injection of 19 pmol/rat or more of salmon calcitonin (sCT) or iodinated sCT suppressed spontaneous intake of food and water in a dose-dependent manner. Tail-whipping was a peculiar behavior which concomitantly developed, but no analgesia ensued from the doses tested (up to 62 pmol/rat). It was examined how the rise and fall pattern of these behavioral effects would correlate with the dispositional pattern of 125I-sCT. When the radioactive peptide was injected in anorectic doses via the i.c.v. route, the radioactivity was found to distribute throughout the brain, but not uniformly. In rats which showed a marked anorexia and tail-whipping behavior, distribution occurred in such a manner that it could be interpreted to reflect the regional and subcellular distribution pattern of sCT-specific binding sites. Even 3 hr after injection, the hypothalamus, the smallest region, retained the highest radioactivity corresponding to about 1% of the dose and at least one half of which was identified as the intact iodo-sCT. To be noted is the finding that sCT injected centrally will quickly enter the systemic circulation and peripherally induced long-lasting hypocalcemia, since the anorectic dose of sCT is considerably higher than the dose needed for the peripheral effect. It is concluded that most of the sCT after i.c.v. injection leaks into the systemic circulation, but the rest is retained rather selectively around the receptor in hypothalamic nuclei for a long time, leading to day-long suppression of feeding and drinking behavior.
脑室内（i.c.v.）注射19 pmol/只或更高剂量的鲑鱼降钙素（sCT）或碘化sCT会以剂量依赖性方式抑制食物和水的自发摄取。甩尾是一种伴随出现的特殊行为，但在所测试的剂量（高达62 pmol/只）下并未产生镇痛作用。研究了这些行为效应的上升和下降模式如何与125I-sCT的分布模式相关。当通过i.c.v.途径以厌食剂量注射放射性肽时，发现放射性分布于整个大脑，但并不均匀。在表现出明显厌食和甩尾行为的大鼠中，放射性的分布方式可以解释为反映了sCT特异性结合位点的区域和亚细胞分布模式。即使在注射后3小时，下丘脑这个最小的区域仍保留着最高的放射性，相当于剂量的约1%，其中至少一半被鉴定为完整的碘代sCT。需要注意的是，中枢注射的sCT会迅速进入体循环并在外周诱导持久的低钙血症，因为sCT的厌食剂量远高于外周效应所需的剂量。结论是，i.c.v.注射后大部分sCT会漏入体循环，但其余部分会在很长一段时间内选择性地保留在下丘脑核受体周围，导致长达一天的摄食和饮水行为抑制。
