Endogenous interstitial adenosine in isolated myenteric neural networks varies inversely with prevailing Po2

Endogenous interstitial adenosine in isolated myenteric neural networks varies inversely with prevailing Po2
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DOI:
10.1152/ajpgi.1999.276.4.g875
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发表时间:
1999-04-01
影响因子:
4.5
通讯作者:
Cook, MA
Cook, MA
中科院分区:
医学2区
文献类型:
--
作者:
Deshpande, NA;McDonald, TJ;Cook, MA

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分离的肌肠神经节网络在浸润方案中用于表征间质腺苷水平对普遍Po-2变化的反应。通过抑制P物质(SP)的释放作为腺苷活性的功能测量来评估这种腺苷的生物活性,并在Po范围内确定O-2张力改变对自发和升高的细胞外K+浓度引起的网络SP释放的影响,从缺氧(Po-2 = 54 mmHg)到高氧(Po-2 = 566 mmHg)的值。SP的释放对Po-2敏感,并呈线性梯度关系。在额外存在腺苷a1受体选择性拮抗剂1,3-二丙基-8-环戊基黄嘌呤(DPCPX)的情况下,灌注显示出相当大的腺苷能抑制,与高氧阈值呈反指数关系。在没有TTX的情况下,DPCPX对诱发SP释放的解除抑制是有TTX时的两倍,表明缺氧时释放的一些腺苷有神经来源。假设的腺苷的神经保护作用与间质腺苷和普遍的O-2张力之间的关系是一致的。
Isolated myenteric ganglion networks were used in a perifusion protocol to characterize the response of interstitial adenosine levels to changes in prevailing Po-2. The biological activity of such adenosine was assessed using inhibition of release of substance P (SP) as a functional measure of adenosine activity, and the effect of altered O-2 tension on both spontaneous and elevated extracellular K+ concentration-evoked SP release from networks was determined over a range of Po, values from hypoxic (Po-2 = 54 mmHg) to hyperoxic (Po-2 = 566 mmHg). Release of SP was found to be sensitive to Po-2, and a linear graded relationship was obtained. Perifusion in the additional presence of the adenosine A1-receptor-selective antagonist 1,3-dipropyl-8-cyclopentyl-xanthine (DPCPX) revealed considerable adenosinergic inhibition with an inverse exponential relationship and hyperoxic threshold Pot. Disinhibition of evoked SP release by DPCPX in the absence of TTX was double that observed in its presence, indicating a neural source for some of the adenosine released during hypoxia. A postulated neuroprotective role for adenosine is consistent with the demonstrated relationship between interstitial adenosine and prevailing O-2 tension.