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腺苷受体激动剂及其他化合物对福斯高林处理的海马切片中环磷酸腺苷积累的影响。

Effect of adenosine receptor agonists and other compounds on cyclic AMP accumulation in forskolin-treated hippocampal slices.

作者信息

Fredholm B B, Jonzon B, Lindström K

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1986 Feb;332(2):173-8. doi: 10.1007/BF00511409.

DOI:10.1007/BF00511409
PMID:3010142
Abstract

The effect of adenosine analogues and some putative neurotransmitters have been studied on cyclic AMP accumulation in rat hippocampal slices treated with the adenylate cyclase activator forskolin. The effects of PGE2 and histamine were potentiated by forskolin (0.1 microM). Isoprenaline and NECA had essentially additive effects with 0.1 microM forskolin and serotonin (above 10(-4) M) inhibited forskolin-stimulated cyclic AMP accumulation. The A1-adenosine receptor selective adenosine analogue R-PIA inhibited forskolin stimulated cyclic AMP accumulation in low doses and stimulated in high. NECA, adenosine and 2-chloroadenosine uniformly stimulated cyclic AMP accumulation. 2',5'-dideoxyadenosine inhibited, but only at high concentrations. Both the stimulatory and the inhibitory effects of R-PIA were antagonized by 8-phenyltheophylline (10 microM). Enprofylline (100 microM) selectively inhibited the stimulatory effect. In the presence of enprofylline both 2-chloroadenosine showed an inhibitory effect on cyclic AMP accumulation. It is concluded that the forskolin-treated rat hippocampal slice is a useful preparation to study both stimulatory and inhibitory effects of transmitters and modulators on adenylate cyclase. The results also show that the rat hippocampus has both A1-receptors that are linked to inhibition of cyclic AMP accumulation and A2-receptors that are linked to stimulation. Furthermore, enprofylline is shown to selectively antagonize the stimulatory response, revealing inhibitory effects of compounds such as 2-chloroadenosine and adenosine.

摘要

研究了腺苷类似物和一些假定的神经递质对用腺苷酸环化酶激活剂福斯高林处理的大鼠海马切片中环磷酸腺苷（cAMP）积累的影响。前列腺素E2（PGE2）和组胺的作用被福斯高林（0.1微摩尔）增强。异丙肾上腺素和N-乙基-5'-氨基-腺苷（NECA）与0.1微摩尔福斯高林具有基本的相加作用，而血清素（高于10^(-4)摩尔）抑制福斯高林刺激的cAMP积累。A1-腺苷受体选择性腺苷类似物R-苯基异丙基腺苷（R-PIA）在低剂量时抑制福斯高林刺激的cAMP积累，在高剂量时则刺激其积累。NECA、腺苷和2-氯腺苷均能刺激cAMP积累。2',5'-二脱氧腺苷仅在高浓度时起抑制作用。R-PIA的刺激和抑制作用均被8-苯基茶碱（10微摩尔）拮抗。恩丙茶碱（100微摩尔）选择性抑制刺激作用。在恩丙茶碱存在的情况下，2-氯腺苷对cAMP积累均表现出抑制作用。得出的结论是，经福斯高林处理的大鼠海马切片是研究递质和调节剂对腺苷酸环化酶的刺激和抑制作用的有用制剂。结果还表明，大鼠海马既有与抑制cAMP积累相关的A1受体，也有与刺激相关的A2受体。此外，恩丙茶碱被证明能选择性拮抗刺激反应，揭示了2-氯腺苷和腺苷等化合物的抑制作用。

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本文引用的文献

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A novel bronchodilator xanthine apparently without adenosine receptor antagonism and tremorogenic effect.一种新型支气管扩张剂黄嘌呤，显然无腺苷受体拮抗作用和致震颤效应。
Eur J Respir Dis. 1983 Jul;64(5):333-9.
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Acta Physiol Scand. 1983 Mar;117(3):461-3. doi: 10.1111/j.1748-1716.1983.tb00022.x.
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Inhibition of brain adenylate cyclase by A1 adenosine receptors: pharmacological characteristics and locations.
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J Mol Neurosci. 1993 Winter;4(4):205-14. doi: 10.1007/BF02821552.
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A1 adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea-pig cerebral cortex.豚鼠大脑皮层中A1腺苷受体对环磷酸腺苷形成及放射性配体结合的抑制作用。
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