Intracerebroventricular injection of 125I-salmon calcitonin in rats: fate, anorexia and hypocalcemia.

Intracerebroventricular injection of 125I-salmon calcitonin in rats: fate, anorexia and hypocalcemia.
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大鼠脑室内注射 125I-鲑鱼降钙素:命运、厌食和低钙血症。

DOI:
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发表时间:
1985
期刊:
Japanese Journal of Pharmacology
影响因子:
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通讯作者:
R. Orlowski
R. Orlowski
中科院分区:
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文献类型:
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作者:
T. Morimoto;M. Okamoto;M. Koida;H. Nakamuta;G. L. Stahl;R. Orlowski

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脑室内(i. c. v.)注射19 pmol/大鼠或更多的鲑鱼降钙素(sCT)或碘化sCT以剂量依赖性方式抑制食物和水的自发摄入。甩尾是一种伴随发生的特殊行为,但试验剂量(高达62 pmol/大鼠)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125 I-sCT的倾向模式相关。当通过i. c. v.途径以厌食剂量注射放射性肽时,发现放射性分布在整个大脑中,但不是均匀的。在表现出明显厌食和甩尾行为的大鼠中,分布发生的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(最小区域)仍保留最高放射性,相当于约1%的剂量,其中至少一半被鉴定为完整的碘-sCT。值得注意的是,发现中央注射的sCT会迅速进入体循环,并在外周引起长期低钙血症,因为sCT的厌食剂量远高于外周效应所需的剂量。可以得出结论,i. c. v.注射后大部分sCT泄漏到体循环中,但其余的是保留在下丘脑核中的受体周围,而选择性的很长一段时间,导致全天抑制进食和饮水行为。
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.