Coates J, Green M A, Sheehan M J, Strong P
Department of Cellular Sciences, Galxo Group Research Ltd, Ware, Herts, UK.
J Pharm Pharmacol. 1994 Nov;46(11):906-10. doi: 10.1111/j.2042-7158.1994.tb05712.x.
Adenosine receptor agonists inhibited electrically-evoked contractions of the rat isolated anococcygeus muscle. The compounds tested were: N6-cyclopentyladenosine (CPA), N((S, trans)-2-hydroxycyclopentyl)adenosine (GR79236), the R- and S-isomers of phenylisopropyladenosine (PIA), 5'-N-ethylcarboxamidoadenosine (NECA), ((2-(4-(2-carboxyethyl)phenyl)ethyl)amino)-N-ethylcarbox-amidoa denosine (CGS 21680) and N-((2-methylphenyl)methyl)adenosine (metrifudil). The rank order of agonist potency was: CPA = R-PIA = GR79236 = NECA >> S-PIA > metrifudil > CGS 21680, which is consistent with an effect mediated by adenosine A1 receptors. A similar rank order of potency was obtained for inhibition of electrically-evoked contractions of the guinea-pig ileum. However, there may be a lower receptor reserve in rat anococcygeus compared with the guinea-pig ileum, since higher concentrations of agonists were necessary to produce effects in the anococcygeus than in the guinea-pig ileum and S-PIA behaved as a partial agonist. The effect of NECA was antagonized in rat anococcygeus and guinea-pig ileum by the mixed A1/A2 receptor antagonist, 8-phenyltheophylline (pA2 values of 6.8 and 6.9, respectively). The selective A1-receptor antagonist, 8-cyclopentyl-1,3- dipropylxanthine (DPCPX), also blocked the inhibitory response to NECA in both tissues. Here, however, the pA2 values (9.6 and 8.6, respectively) were slightly but significantly different. These values confirm that the prejunctional adenosine receptors of the rat anococcygeus are of the A1 type, and suggest that they are similar but not necessarily identical to those of the guinea-pig ileum. The differing potencies of DPCPX as an antagonist of NECA between the preparations may reflect a tissue-dependent variation in sensitivity to this antagonist.
腺苷受体激动剂可抑制大鼠离体肛门尾骨肌的电诱发收缩。所测试的化合物有：N6-环戊基腺苷（CPA）、N-((S,反式)-2-羟基环戊基)腺苷（GR79236）、苯异丙基腺苷（PIA）的R-和S-异构体、5'-N-乙基羧酰胺腺苷（NECA）、((2-(4-(2-羧乙基)phenyl)乙基)氨基)-N-乙基羧酰胺腺苷（CGS 21680）和N-((2-甲基苯基)甲基)腺苷（美曲氟地尔）。激动剂效力的排序为：CPA = R-PIA = GR79236 = NECA >> S-PIA > 美曲氟地尔 > CGS 21680，这与腺苷A1受体介导的效应一致。在抑制豚鼠回肠的电诱发收缩方面也获得了类似的效力排序。然而，与豚鼠回肠相比，大鼠肛门尾骨肌中的受体储备可能较低，因为在肛门尾骨肌中产生效应所需的激动剂浓度高于豚鼠回肠，且S-PIA表现为部分激动剂。在大鼠肛门尾骨肌和豚鼠回肠中，NECA的效应被A1/A2受体混合拮抗剂8-苯基茶碱拮抗（pA2值分别为6.8和6.9）。选择性A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）也阻断了两种组织中对NECA的抑制反应。然而，此处的pA2值（分别为9.6和8.6）略有但显著不同。这些值证实大鼠肛门尾骨肌的节前腺苷受体为A1型，并表明它们与豚鼠回肠的受体相似但不一定相同。制剂之间DPCPX作为NECA拮抗剂的效力不同可能反映了对该拮抗剂敏感性的组织依赖性差异。
