Maya-Núñez G, Castro-Fernández C, Méndez J P
Research Unit in Developmental Biology, Hospital de Pediatría, Centro Médico Nacional Siglo SXXI, Instituto Mexicano del Seguro Social, Mexico.
Endocrine. 2005 Jun;27(1):67-73. doi: 10.1385/endo:27:1:067.
Corticotropin-releasing hormone (CRH) is one of the major proteins responsible for brain stress regulation. Two well-known receptors have been described: type 1 and type 2alpha, both members of the receptor superfamily of G protein-coupled receptors (GPCR). We investigated receptor regulation when both CRH receptor subtypes are coexpressed in the same mammalian cell line. When both types of receptors are coexpressed, cAMP second messenger production is partially inhibited compared to when receptors are expressed separately. However, neither binding kinetics nor internalization rates are modified by coexpression of these receptors. To our knowledge this is the first demonstration of receptor interaction that results in the modification of CRH-mediated signal transduction pathway. Because CRH-R1 and CRH-R2alpha have overlapping mRNA expression patterns in the brain, these receptors may be coexpressed in neurons, suggesting that receptor interaction may play an important role in the effect evoked by CRH, contributing to the complexity of differential coupling of the CRH receptors in different endocrine and stress behavior responses.
促肾上腺皮质激素释放激素（CRH）是负责大脑应激调节的主要蛋白质之一。已描述了两种著名的受体：1型和2α型，它们都是G蛋白偶联受体（GPCR）超家族的成员。我们研究了两种CRH受体亚型在同一哺乳动物细胞系中共表达时的受体调节情况。当两种类型的受体共表达时，与单独表达受体相比，cAMP第二信使的产生受到部分抑制。然而，这些受体的共表达并未改变结合动力学或内化速率。据我们所知，这是首次证明受体相互作用导致CRH介导的信号转导途径发生改变。由于CRH-R1和CRH-R2α在大脑中具有重叠的mRNA表达模式，这些受体可能在神经元中共表达，这表明受体相互作用可能在CRH诱发的效应中起重要作用，有助于CRH受体在不同内分泌和应激行为反应中差异偶联的复杂性。
