Digestive Diseases Branch, National Institutes of Health, Bethesda, Maryland 20892; and Laboratory of Biological Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892.
Mol Cell Neurosci. 1993 Apr;4(2):143-54. doi: 10.1006/mcne.1993.1018.
Cholecystokinin (CCK) is one of the most abundant peptides in the central nervous system (CNS). Radioligand-binding studies have identified and localized both central (CCK(B)-R) and peripheral (CCK(A)-R) receptor subtypes in the CNS. However, these studies have been limited by the relative specificities of agonists and antagonists for receptor subtypes and their inability to distinguish cell bodies from dendritic projection. Recently, we isolated and cloned the cDNAs for both CCK(A) and CCK(B) receptors. In the present study, (35)S-labeled cRNA antisense probes were synthesized for both receptors and in situ hybridization studies were performed in the rat brain, allowing a direct and independent comparison of the distinct distribution of expression of CCK(A) and CCK(B) receptor mRNAs in the rat brain for the first time. mRNAs for both CCK(A) and CCK(B) receptors were expressed mainly in the cortex, olfactory regions, hippocampal formation, septum, and interpeduncular nucleus. Only CCK(A) receptor mRNAs were expressed in some of the hypothalamic nuclei (paraventricular nucleus, arcuate nucleus, and medial preoptic area). In most of amygdaloid nuclei only CCK(B) receptor mRNAs were expressed. Although the presence of receptor mRNAs does not necessarily imply the presence of functional receptor proteins in the same location, this study showed the regional distribution of mRNAs for CCK(A) and CCK(B) receptors and provides important information about the distribution of CCK receptor subtypes in the CNS which will allow better resolution of their functional roles in the brain.
胆囊收缩素（CCK）是中枢神经系统（CNS）中最丰富的肽之一。放射配体结合研究已经鉴定和定位了中枢（CCK（B）-R）和外周（CCK（A）-R）受体亚型在中枢神经系统中。然而，这些研究受到激动剂和拮抗剂对受体亚型的相对特异性以及它们无法区分细胞体和树突投射的限制。最近，我们分离并克隆了 CCK（A）和 CCK（B）受体的 cDNA。在本研究中，我们为这两种受体合成了（35）S 标记的 cRNA 反义探针，并在大鼠脑中进行了原位杂交研究，首次直接和独立地比较了 CCK（A）和 CCK（B）受体 mRNA 在大鼠脑中的表达分布。CCK（A）和 CCK（B）受体的 mRNA 主要在皮质、嗅觉区域、海马结构、隔区和脚间核中表达。只有 CCK（A）受体的 mRNA 在一些下丘脑核（室旁核、弓状核和视前内侧区）中表达。在大多数杏仁核核中仅表达 CCK（B）受体的 mRNA。尽管受体 mRNA 的存在并不一定意味着在同一位置存在功能性受体蛋白，但这项研究显示了 CCK（A）和 CCK（B）受体的 mRNA 在大脑中的分布，并为 CCK 受体亚型在中枢神经系统中的分布提供了重要信息，这将有助于更好地确定它们在大脑中的功能作用。
