Chessell I P, Michel A D, Humphrey P P
Glaxo Institute of Applied Pharmacology, University of Cambridge, U.K.
Neuroscience. 1997 Apr;77(3):783-91. doi: 10.1016/s0306-4522(96)00523-4.
Extracellular recording techniques were used in brain slices to characterize excitatory responses produced by purine nucleotides in the rat medial vestibular nucleus, an area where functional purinoceptors have not previously been described. In the continued presence of the adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine, which alone caused a small increase in the spontaneous firing rate, the P2 purinoceptor agonists alpha,beta-methyleneadenosine 5'-triphosphate (alphabeta meATP) and adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS) caused concentration-dependent increases in spontaneous firing rate, with EC50 values of 41.8 and 1.7 microM, respectively. Only approximately 35% of all neurons studied displayed excitatory responses to these agents. Responses waned in the continued presence of high concentrations of the latter, but not the former agonist. Furthermore, in the continued presence of a maximal concentration of alphabeta meATP, ADPbetaS produced further increases in the firing rate of these neurons. The P2 antagonist, suramin, ablated responses to alphabeta meATP, but did not affect responses to ADPbetaS, whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid antagonized responses to both agonists. The nucleotide analogue alpha,beta-methyleneadenosine 5'-diphosphate, which displays affinity for putative P2X receptors in brain, also produced concentration-dependent increases in firing frequency, which were also markedly antagonized in the presence of suramin, this agonist being only slightly less potent than alphabeta meATP. In conclusion, a subpopulation of rat medial vestibular neuronal responses mediated by both P2X and P2Y purinoceptors can be distinguished. Comparison of their properties with those of recombinantly expressed P2X and P2Y receptors suggests that these endogenous P2 purinoceptor types differ in several important aspects from heterologously expressed recombinant receptors identified from cloning studies.
细胞外记录技术被用于脑片，以表征嘌呤核苷酸在大鼠内侧前庭核中产生的兴奋性反应，该区域此前尚未描述过功能性嘌呤受体。在腺苷拮抗剂8-环戊基-1,3-二丙基黄嘌呤持续存在的情况下（其单独作用会使自发放电率略有增加），P2嘌呤受体激动剂α,β-亚甲基腺苷5'-三磷酸（αβ meATP）和腺苷5'-O-(2-硫代二磷酸)（ADPβS）会使自发放电率呈浓度依赖性增加，其半数有效浓度（EC50）值分别为41.8和1.7微摩尔。在所有研究的神经元中，只有约35%对这些药物表现出兴奋性反应。在高浓度的后一种激动剂（而非前一种激动剂）持续存在的情况下，反应会逐渐减弱。此外，在αβ meATP的最大浓度持续存在的情况下，ADPβS会使这些神经元的放电率进一步增加。P2拮抗剂苏拉明消除了对αβ meATP的反应，但不影响对ADPβS的反应，而磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸则拮抗了对两种激动剂的反应。核苷酸类似物α,β-亚甲基腺苷5'-二磷酸对脑中假定的P2X受体具有亲和力，也会使放电频率呈浓度依赖性增加，在苏拉明存在的情况下这种增加也会受到明显拮抗，该激动剂的效力仅略低于αβ meATP。总之，可以区分出由P2X和P2Y嘌呤受体介导的大鼠内侧前庭神经元反应的一个亚群。将它们的特性与重组表达的P2X和P2Y受体的特性进行比较表明，这些内源性P2嘌呤受体类型在几个重要方面与从克隆研究中鉴定出的异源表达重组受体不同。
