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首页> 外文期刊>British Journal of Pharmacology >Effects of pH on responses to adenosine, CGS 21680, carbachol and nitroprusside in the isolated perfused superior mesenteric arterial bed of the rat
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Effects of pH on responses to adenosine, CGS 21680, carbachol and nitroprusside in the isolated perfused superior mesenteric arterial bed of the rat

机译：pH对大鼠离体灌注肠系膜上动脉床中腺苷，CGS 21680，卡巴胆碱和硝普钠反应的影响

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1 The receptors mediating the vasodilator responses to adenosine in the isolated mesenteric arterial bed of the rat were identified by use of selective agonists and antagonists and the involvement of the endothelium was examined. 2 Adenosine-mediated dilatation of the mesentery was potentiated by the nitric oxide synthase inhibitor, N~G-nitro-L-arginine methyl ester (L-NAME, 100 μM), but in contrast, removal of the endothelium substantially reduced the responses to adenosine. 3 The order of potency of adenosine receptor agonists was: 5′-N-ethylcarboxamidoadenosine (NECA) > 2-p-(-2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) > 2-chloro-N~6-cyclopentyl-adenosine (CCPA) ≥ adenosine, suggesting the presence of A_(2A) receptors. 4 Adenosine-mediated dilatation was inhibited by the non-selective adenosine receptor antagonist, 8-phenyltheophylline (3 μM) and by the A_(2A) receptor antagonist 8-(3-chlorostyryl)caffeine (500 nM), but was unaffected by the A_1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM). 5 Reducing the pH of the perfusate to 6.8 potentiated the actions of both CGS 21680 and adenosine, but the vasodilator effects of carbachol were the same at both pH values. The adenosine response at the lower pH as at pH 7.4, was unaffected by DPCPX. The actions of the nitrovasodilator, sodium nitroprusside, were also potentiated at pH 6.8 relative to those at the higher pH value but smaller responses were obtained at the lower pH value with forskolin, a stimulator of adenylyl cyclase, than at pH 7.4. 6 It is concluded that the adenosine receptor mediating dilatation of the rat mesenteric arterial bed is of the A_(2A) subtype, that the response, under the conditions used, is apparently partly dependent on the endothelium (but not due to the release of nitric oxide), and that the response to activation of this receptor is potentiated by a reduction in pH which is similar to that seen in ischaemic conditions.
机译：1通过使用选择性激动剂和拮抗剂鉴定了介导大鼠离体肠系膜动脉床中血管舒张剂对腺苷反应的受体，并检查了内皮的参与。 2一氧化氮合酶抑制剂N〜G-硝基-L-精氨酸甲酯（L-NAME，100μM）增强了腺苷介导的肠系膜扩张，但相比之下，去除内皮可显着降低对腺苷。 3腺苷受体激动剂的效力顺序为：5'-N-乙基羧酰胺基腺苷（NECA）> 2-对-（-2-羧乙基）苯乙基氨基5'-N-乙基羧酰胺基腺苷（CGS 21680）> 2-氯-N〜 6-环戊基腺苷（CCPA）≥腺苷，表明存在A_（2A）受体。 4腺苷介导的扩张受非选择性腺苷受体拮抗剂8-苯基茶碱（3μM）和A_（2A）受体拮抗剂8-（3-氯苯乙烯基）咖啡因（500 nM）抑制，但不受A_1受体拮抗剂1，3-二丙基-8-环戊基黄嘌呤（DPCPX; 10 nM）。 5将灌注液的pH值降低到6.8增强了CGS 21680和腺苷的作用，但是在两个pH值下，卡巴胆碱的血管舒张作用均相同。在较低的pH值（如pH 7.4）下，腺苷反应不受DPCPX的影响。相对于较高pH值，硝化舒张剂硝普钠的作用在pH 6.8时也得到增强，但是在较低pH值下，腺苷酸环化酶的刺激剂forskolin与pH 7.4相比，反应较小。 6结论是，介导大鼠肠系膜动脉床扩张的腺苷受体属于A_（2A）亚型，在所使用的条件下，响应显然部分取决于内皮（但不是由于硝酸的释放）氧化物），并且通过降低pH来增强对该受体激活的反应，类似于在缺血条件下观察到的那样。

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