Department of Medicine (Neurology) and Centre for Neuroscience, University of Alberta, Edmonton, AB, Canada.
Eur J Neurosci. 2009 Oct;30(8):1585-93. doi: 10.1111/j.1460-9568.2009.06956.x. Epub 2009 Oct 12.
Prolactin-releasing peptide (PrRP), an RF amide peptide present in the brain, generates a wide variety of centrally generated autonomic responses, including increases in arterial blood pressure and heart rate. The identity of the receptor mediating the effects of PrRP is unknown. In addition to GPR10, which is its putative endogenous receptor, PrRP demonstrates a high binding affinity for Neuropeptide FF (NPFF) receptors, specifically the NPFF2 receptor. In the present study, we examined whether the central cardiovascular effects of PrRP in the intact animal and its cellular effects on parvocellular paraventricular nucleus (PVN) neurons are mediated via NPFF receptors. In conscious rats, intracerebroventricular (i.c.v.) PrRP caused an increase in arterial blood pressure and heart rate, which was blocked with RF9, a specific NPFF receptor antagonist. These PrRP-evoked cardiovascular effects were preserved in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat strain, in which the GRP10 receptor gene was mutated. In rat brain slices, whole-cell patch clamp recordings of parvocellular paraventricular nucleus neurons show PrRP caused a decrease in evoked and miniature GABAergic inhibitory postsynaptic currents (IPSCs), effects that were antagonized by RF9, but not neuropeptide Y, a putative GPR10 receptor antagonist. The effects of PrRP on IPSCs in OLETF rats were similar to those in wild-type rats. Both in vivo and in vitro data strongly suggest that certain PrRP effects in the brain are expressed via NPFF receptors, probably NPFF2, rather than the GPR10 receptor. These observations may assume clinical relevance as RF amide peptides such NPFF and PrRP become therapeutic targets for a variety of autonomically related disorders.
促泌乳素释放肽（PrRP）是一种存在于大脑中的 RF 酰胺肽，可产生广泛的中枢自主反应，包括动脉血压和心率升高。介导 PrRP 作用的受体的身份尚不清楚。除了其假定的内源性受体 GPR10 外，PrRP 还表现出对神经肽 FF（NPFF）受体，特别是 NPFF2 受体的高结合亲和力。在本研究中，我们研究了 PrRP 在完整动物中的中枢心血管作用及其对小细胞室旁核（PVN）神经元的细胞作用是否通过 NPFF 受体介导。在清醒大鼠中，脑室内（i.c.v.）给予 PrRP 可引起动脉血压和心率升高，这可被特定的 NPFF 受体拮抗剂 RF9 阻断。在 GRP10 受体基因发生突变的 Otsuka Long-Evans Tokushima Fatty（OLETF）大鼠品系中，保留了这些 PrRP 引起的心血管作用。在大鼠脑切片中，全细胞膜片钳记录小细胞室旁核神经元显示 PrRP 可引起诱发和微小 GABA 能抑制性突触后电流（IPSCs）减少，这些作用可被 RF9 拮抗，但不能被神经肽 Y 拮抗，神经肽 Y 是一种假定的 GPR10 受体拮抗剂。在 OLETF 大鼠中，PrRP 对 IPSC 的作用与野生型大鼠相似。体内和体外数据均强烈表明，脑内的某些 PrRP 作用是通过 NPFF 受体表达的，可能是 NPFF2，而不是 GPR10 受体。这些观察结果可能具有临床相关性，因为 RF 酰胺肽（如 NPFF 和 PrRP）成为各种与自主相关的疾病的治疗靶点。
