Borowsky B, Adham N, Jones K A, Raddatz R, Artymyshyn R, Ogozalek K L, Durkin M M, Lakhlani P P, Bonini J A, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa F Y, Branchek T A, Gerald C
Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):8966-71. doi: 10.1073/pnas.151105198. Epub 2001 Jul 17.
Tyramine, beta-phenylethylamine, tryptamine, and octopamine are biogenic amines present in trace levels in mammalian nervous systems. Although some "trace amines" have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Using a degenerate PCR approach, we have identified 15 G protein-coupled receptors (GPCR) from human and rodent tissues. Together with the orphan receptor PNR, these receptors form a subfamily of rhodopsin GPCRs distinct from, but related to the classical biogenic amine receptors. We have demonstrated that two of these receptors bind and/or are activated by trace amines. The cloning of mammalian GPCRs for trace amines supports a role for trace amines as neurotransmitters in vertebrates. Three of the four human receptors from this family are present in the amygdala, possibly linking trace amine receptors to affective disorders. The identification of this family of receptors should rekindle the investigation of the roles of trace amines in mammalian nervous systems and may potentially lead to the development of novel therapeutics for a variety of indications.
酪胺、β-苯乙胺、色胺和章鱼胺是哺乳动物神经系统中微量存在的生物胺。尽管一些“痕量胺”在无脊椎动物中作为神经递质的作用已明确界定，但它们在脊椎动物中作为真正神经递质发挥作用的程度仍属推测。我们采用简并PCR方法，从人和啮齿动物组织中鉴定出15种G蛋白偶联受体（GPCR）。这些受体与孤儿受体PNR一起，形成了视紫红质GPCR的一个亚家族，与经典生物胺受体不同但相关。我们已证明其中两种受体可与痕量胺结合和/或被痕量胺激活。哺乳动物痕量胺GPCR的克隆支持了痕量胺在脊椎动物中作为神经递质的作用。该家族的四个人类受体中有三个存在于杏仁核中，这可能将痕量胺受体与情感障碍联系起来。这一家族受体的鉴定应会重新激发对痕量胺在哺乳动物神经系统中作用的研究，并可能潜在地导致开发针对多种适应症的新型疗法。
