Volkoff H, Peter R E
Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
Endocrinology. 2001 Dec;142(12):5076-88. doi: 10.1210/endo.142.12.8519.
Complementary DNAs encoding two forms of cocaine- and amphetamine-regulated transcript (CART) peptide precursors were identified from goldfish brain and named CART I and CART II. Each cDNA contains a signal peptide sequence, the putative CART-like peptide, and a carboxy-terminal extension peptide. Form I encodes a 117-amino acid pro-CART, whereas form II encodes a 120-amino acid pro-CART. Both forms resemble mammalian CART peptides. Each goldfish CART precursor is encoded by three exons interrupted by two introns within genomic DNA. RT-PCR, slot blot, and Northern blot analysis showed that the mRNAs for form I and II precursors have a widespread distribution. Form I and II are present in the brain, pituitary, eye, gonads, and kidney. Form I is also present in the gill. In the brain, form I is predominant in the olfactory bulb and hypothalamus, and form II is predominant in the optic tectum. Food deprivation for 96 h induced a decrease in form I mRNA levels in the telencephalon-preoptic region, hypothalamus, and olfactory bulb and in form II mRNA expression in the olfactory bulb. An increase in mRNA levels was observed 2 h following a meal in the olfactory bulbs and hypothalamus for form I whereas no postprandial changes in form II mRNA levels were observed. Intracerebroventricular injections of human CART alone induced a significant decrease in food intake. Injections of leptin reinforced the inhibition of feeding behavior and food intake seen in CART-treated fish. Central injection of leptin induced an increase in CART I mRNA in the optic tectum, hypothalamus, and olfactory bulbs but had no effect on CART II mRNA expression in the brain. These results suggest that CART peptides act as leptin-regulated satiety factors in goldfish and that they might have other physiological roles besides feeding, possibly in sensory information processing.
从金鱼脑中鉴定出编码两种形式的可卡因和苯丙胺调节转录物（CART）肽前体的互补DNA，并将其命名为CART I和CART II。每个cDNA都包含一个信号肽序列、假定的CART样肽和一个羧基末端延伸肽。I型编码一个117个氨基酸的前CART，而II型编码一个120个氨基酸的前CART。两种形式都类似于哺乳动物的CART肽。每个金鱼CART前体由基因组DNA中的三个外显子编码，中间被两个内含子隔开。逆转录聚合酶链反应（RT-PCR）、斑点印迹和Northern印迹分析表明，I型和II型前体的mRNA分布广泛。I型和II型存在于脑、垂体、眼睛、性腺和肾脏中。I型也存在于鳃中。在脑中，I型在嗅球和下丘脑中占主导地位，而II型在视顶盖中占主导地位。禁食96小时导致端脑-视前区、下丘脑和嗅球中I型mRNA水平降低，嗅球中II型mRNA表达降低。进食后2小时，嗅球和下丘脑中I型mRNA水平升高，而II型mRNA水平未观察到餐后变化。脑室内注射人CART单独诱导食物摄入量显著减少。注射瘦素增强了CART处理的鱼中摄食行为和食物摄入量的抑制。中枢注射瘦素诱导视顶盖、下丘脑和嗅球中CART I mRNA增加，但对脑中CART II mRNA表达无影响。这些结果表明，CART肽在金鱼中作为瘦素调节的饱腹感因子起作用，并且它们可能除了进食外还具有其他生理作用，可能在感觉信息处理中发挥作用。
