Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
Neuroscience. 2010 Mar 17;166(2):671-9. doi: 10.1016/j.neuroscience.2010.01.001. Epub 2010 Jan 6.
Agonists of ghrelin receptors can lower or elevate blood pressure, and it has been suggested that the increases in blood pressure are caused by actions at receptors in the spinal cord. However, this has not been adequately investigated, and the locations of neurons in the spinal cord that express ghrelin receptors, through which blood pressure increases may be exerted, are not known. We investigated the effects within the spinal cord of two non-peptide ghrelin receptor agonists, GSK894490 and CP464709, and two peptide receptor agonists, ghrelin and des-acyl ghrelin, and we used polymerase chain reaction (PCR) and in situ hybridization to examine ghrelin receptor expression. I.v. application of the non-peptide ghrelin receptor agonists caused biphasic changes in blood pressure, a brief drop followed by a blood pressure increase that lasted several minutes. The blood pressure rise, but not the fall, was antagonized by i.v. hexamethonium. Application of these agonists or ghrelin peptide directly to the spinal cord caused only a blood pressure increase. Des-acyl ghrelin had no significant action. The maximum pressor effects of agonists occurred with application at spinal cord levels T9 to T12. Neither i.v. nor spinal cord application of the agonists had significant effect on heart rate or the electrocardiogram. Ghrelin receptor gene expression was detected by PCR and in situ hybridization. In situ hybridization localized expression to neurons, including autonomic preganglionic neurons of the intermediolateral cell columns at all levels from T3 to S2. The numbers of ghrelin receptor expressing neurons in the intermediolateral cell columns were similar to the numbers of nitric oxide synthase positive neurons, but there was little overlap between these two populations. We conclude that activation of excitatory ghrelin receptors on sympathetic preganglionic neurons increases blood pressure, and that decreases in blood pressure caused by ghrelin agonists are mediated through receptors on blood vessels.
胃饥饿素受体激动剂可降低或升高血压，有人提出，血压升高是由于脊髓受体的作用所致。然而，这尚未得到充分研究，也不知道表达胃饥饿素受体的脊髓神经元的位置，通过这些神经元可能发挥了血压升高的作用。我们研究了两种非肽类胃饥饿素受体激动剂，GSK894490 和 CP464709，以及两种肽类受体激动剂，胃饥饿素和去酰基胃饥饿素，在脊髓内的作用，我们使用聚合酶链反应（PCR）和原位杂交来检查胃饥饿素受体的表达。静脉内应用非肽类胃饥饿素受体激动剂可引起血压的双相变化，短暂下降后血压升高持续数分钟。血压升高，但不是下降，被静脉内给予六烃季铵所拮抗。这些激动剂或胃饥饿素肽直接应用于脊髓仅引起血压升高。去酰基胃饥饿素没有明显作用。激动剂的最大升压作用发生在脊髓 T9 至 T12 水平。静脉内或脊髓内应用激动剂对心率或心电图均无明显影响。PCR 和原位杂交检测到胃饥饿素受体基因表达。原位杂交将表达定位于神经元，包括从 T3 到 S2 的所有水平的中间外侧细胞柱中的自主节前神经元。中间外侧细胞柱中的胃饥饿素受体表达神经元的数量与一氧化氮合酶阳性神经元的数量相似，但这两个群体之间几乎没有重叠。我们的结论是，兴奋型胃饥饿素受体在交感节前神经元上的激活增加了血压，而胃饥饿素激动剂引起的血压下降是通过血管上的受体介导的。
