RELEASE OF NUCLEOSIDES AND NUCLEOTIDES FROM THE RABBIT HEART BY SYMPATHETIC-NERVE STIMULATION
RELEASE OF NUCLEOSIDES AND NUCLEOTIDES FROM THE RABBIT HEART BY SYMPATHETIC-NERVE STIMULATION
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DOI：
10.1111/j.1748-1716.1982.tb07142.x
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
WENNMALM, M
中科院分区：
文献类型：
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作者：
FREDHOLM, BB;HEDQVIST, P;WENNMALM, M
The release of endogenous purine compounds from the isolated Langendorff perfused heart during sympathetic nerve stimulation was studied. The contents of adenosine, inosine, hypoxanthine and AMP in heart muscle and in the perfusate were studied by HPLC [high-performance liquid chromatography]. Adenosine or AMP, administered via the perfusate, was rapidly inactivated by the heart. The recovery of adenosine after a single passage was 13% and that of AMP, 40%. The recovery of adenosine was increased by inhibitors of adenosine deaminase or nucleoside uptake; that of AMP by inhibition of ecto-5''-nucleotidase. The efflux of adenosine and, especially, inosine was increased by sympathetic nerve stimulation in a time- and frequency-dependent manner. Simultaneously, the tissue level of the 2 nucleosides increased. Nerve stimulation did not enhance AMP efflux in the absence of drugs and did not significantly enhance tissue AMP levels. The effect of sympathetic nerve stimulation was mimicked by noradrenaline [norepinephrine] and was blocked by adrenoceptor-blocking agents. The release of adenosine induced by nerve stimulation was enhanced by uptake inhibitors and by an inhibitor of adenosine deaminase. The release of inosine was simultaneously reduced. In the presence of an inhibitor of ecto-5''-nucleotidase, nerve stimulation induced a significant release of AMP, but no significant alteration in the release of adenosine or inosine was found. Sympathetic nerve stimulation leads to release of both adenine nucleotides and adenosine from the perfused rabbit heart. These substances are rapidly catabolized by 5''-nucleotidase and by uptake followed by deamination, respectively, to form mainly inosine. The release of adenosine may reflect the energy state of the cardiac cells, while the nucleotide release may depend on depolarization.
