Cunha R A, Sebastião A M
Gulbenkian Institute of Science, Laboratory of Pharmacology, Oeiras Codex, Portugal.
Eur J Pharmacol. 1991 May 2;197(1):83-92. doi: 10.1016/0014-2999(91)90368-z.
The effects of coformycin, alpha,beta-methylene ADP, dipyridamole in the absence and presence of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), nitrobenzylthioinosine (NBTI), mioflazine and ouabain on the metabolic pathways of exogenously applied ATP and its metabolites in the frog innervated sartorius muscle were investigated. ATP catabolism yielded ADP, AMP, IMP, adenosine and inosine; the ecto-ATPase in situ was shown to be Ca(2+)- or Mg(2+)-activated with a Kmapp for ATP of 767 +/- 48 microM. AMP catabolism yielded IMP, adenosine and inosine; inosine was formed from either exogenous IMP or exogenous adenosine. Catabolism of AMP into IMP was blocked by coformycin, which enhanced adenosine and inosine formation from AMP. alpha,beta-Methylene ADP blocked adenosine formation from AMP and inosine formation from IMP; formation of IMP from AMP was enhanced by alpha,beta-methylene ADP. Complete blockade of AMP degradation was achieved with the simultaneous use of coformycin and alpha,beta-methylene ADP. Dipyridamole attenuated but did not completely block extracellular adenosine removal and inosine appearance in the bath. EHNA, applied in the presence of dipyridamole, did not cause any further attenuation of extracellular adenosine removal. Mioflazine, NBTI and ouabain did not affect adenosine disappearance from the bath. The results suggest that, in the frog innervated sartorius muscle, ATP can be sequentially catabolized into AMP which is then catabolized either into IMP or into adenosine. This extracellular degradation of AMP into IMP might then constitute a shunt-like mechanism to control the levels of adenosine formed from adenine nucleotides.
研究了助间霉素、α,β-亚甲基二磷酸腺苷、双嘧达莫在不存在和存在赤藓红-9-(2-羟基-3-壬基)腺嘌呤（EHNA）、硝基苄硫基肌苷（NBTI）、米氟嗪和哇巴因的情况下，对蛙神经支配的缝匠肌中外源性应用的ATP及其代谢产物代谢途径的影响。ATP分解代谢产生ADP、AMP、IMP、腺苷和肌苷；原位外切ATP酶显示为Ca(2+)或Mg(2+)激活，ATP的Kmapp为767±48μM。AMP分解代谢产生IMP、腺苷和肌苷；肌苷由外源性IMP或外源性腺苷形成。助间霉素阻断了AMP分解为IMP，这增强了AMP形成腺苷和肌苷。α,β-亚甲基二磷酸腺苷阻断了AMP形成腺苷以及IMP形成肌苷；α,β-亚甲基二磷酸腺苷增强了AMP形成IMP。同时使用助间霉素和α,β-亚甲基二磷酸腺苷可完全阻断AMP降解。双嘧达莫减弱但未完全阻断浴槽中细胞外腺苷的清除和肌苷的出现。在双嘧达莫存在的情况下应用EHNA，并未导致细胞外腺苷清除的进一步减弱。米氟嗪、NBTI和哇巴因不影响浴槽中腺苷的消失。结果表明，在蛙神经支配的缝匠肌中，ATP可依次分解代谢为AMP，然后AMP再分解代谢为IMP或腺苷。AMP向IMP的这种细胞外降解可能构成一种类似分流的机制，以控制由腺嘌呤核苷酸形成的腺苷水平。
