School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Br J Pharmacol. 2013 Feb;168(3):746-60. doi: 10.1111/j.1476-5381.2012.02177.x.
Hyper-nociceptive PGE(2) EP(4) receptors and prostacyclin (IP) receptors are present in adult rat dorsal root ganglion (DRG) neurones and glial cells in culture. The present study has investigated the cell-specific expression of two other G(s) -protein coupled hyper-nociceptive receptor systems: β-adrenoceptors and calcitonin gene-related peptide (CGRP) receptors in isolated DRG cells and has examined the influence of neurone-glial cell interactions in regulating adenylyl cyclase (AC) activity.
Agonist-stimulated AC activity was determined in mixed DRG cell cultures from adult rats and compared with activity in DRG neurone-enriched cell cultures and pure DRG glial cell cultures.
Pharmacological analysis showed the presence of G(s) -coupled β(2) -adrenoceptors and CGRP receptors, but not β(1) -adrenoceptors, in all three DRG cell preparations. Agonist-stimulated AC activity was weakest in DRG neurone-enriched cell cultures. DRG neurones inhibited IP receptor-stimulated glial cell AC activity by a process dependent on both cell-cell contact and neurone-derived soluble factors, but this is unlikely to involve purine or glutamine receptor activation.
G(s) -coupled hyper-nociceptive receptors are readily expressed on DRG glial cells in isolated cell cultures and the activity of CGRP, EP(4) and IP receptors, but not β(2) -adrenoceptors, in glial cells is inhibited by DRG neurones. Studies using isolated DRG cells should be aware that hyper-nociceptive ligands may stimulate receptors on glial cells in addition to neurones, and that variable numbers of neurones and glial cells will influence absolute measures of AC activity and affect downstream functional responses.
在成年大鼠背根神经节（DRG）神经元和神经胶质细胞的培养物中存在超敏前列腺素 E2（PGE2）EP4 受体和前列环素（IP）受体。本研究调查了另外两个 Gs-蛋白偶联超敏受体系统：β-肾上腺素能受体和降钙素基因相关肽（CGRP）受体在分离的 DRG 细胞中的细胞特异性表达，并研究了神经元-神经胶质细胞相互作用对腺苷酸环化酶（AC）活性的调节作用。
在成年大鼠混合 DRG 细胞培养物中测定激动剂刺激的 AC 活性，并与 DRG 神经元丰富的细胞培养物和纯 DRG 神经胶质细胞培养物的活性进行比较。
药理学分析表明，在所有三种 DRG 细胞制剂中均存在 Gs-偶联的β2-肾上腺素能受体和 CGRP 受体，但不存在β1-肾上腺素能受体。在 DRG 神经元丰富的细胞培养物中，激动剂刺激的 AC 活性最弱。DRG 神经元通过依赖于细胞-细胞接触和神经元衍生的可溶性因子的过程抑制 IP 受体刺激的神经胶质细胞 AC 活性，但这可能不涉及嘌呤或谷氨酰胺受体激活。
在分离的细胞培养物中，G 蛋白偶联的超敏受体很容易在 DRG 神经胶质细胞上表达，CGRP、EP4 和 IP 受体的活性（但β2-肾上腺素能受体的活性除外）在神经胶质细胞中被 DRG 神经元抑制。使用分离的 DRG 细胞的研究应该意识到，除了神经元之外，超敏配体可能会刺激神经胶质细胞上的受体，并且神经元和神经胶质细胞的数量变化将影响 AC 活性的绝对测量值，并影响下游功能反应。
