Subclassification of Neuronal Adenosine Receptors
Subclassification of Neuronal Adenosine Receptors
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神经元腺苷受体的亚分类
DOI：
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发表时间：
1990
期刊：
影响因子：
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通讯作者：
L. Stelius
中科院分区：
文献类型：
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作者：
L. Gustafsson;C. Wiklund;N. Wiklund;L. Stelius
已经提出腺苷通过两种不同的受体亚类发挥其细胞外生物学效应：介导腺苷酸环化酶抑制的A1受体和介导环化酶刺激的A2受体。除了它们对腺苷酸环化酶的相反作用外，对于某些腺苷类似物，受体具有不同的结构活性关系。在A_1受体上，其作用顺序为N_6-R-苯基异丙基腺苷（R-PIA）≥ S ′-N-乙基甲酰胺腺苷（NECA）> S-PIA，而在A_2受体上，其作用顺序为NECA > R-PIA ≥ S-PIA。Stone 1985，Wiklund et al. 1989 b）。腺苷酸环化酶的刺激或抑制不再被视为受体类型的安全标准（Stone 1985）。提出了将A2受体进一步细分为A2 a和A2 b，其中A2 a是高亲和力受体（EC 50纳摩尔范围），A2 b是低亲和力受体（EC 50微摩尔范围）（参见图11）。Bruns等人，1987年）。研究表明，腺苷受体的激动剂特性不符合A1和A2受体的定义，并提出了一类新的腺苷受体：A3（Ribeiro & Rechtiao 1986）。我们以前曾报道过自主神经上的腺苷A1受体与CNS中的腺苷A1受体在结构活性关系上的差异（Gustafsson等，1985，1989; Wiklund等，1989 a）。本研究描绘的突触前P1受体在自主节后神经作为明确的A1型，并可能构成一个新的亚类，A1 b。
It has been proposed that adenosine exerts its extracellular biological effects via two distinct receptor subclasses: A1 which mediate inhibition of adenylate cyclase and A2 receptors which mediate stimulation of the cyclase. In addition to their opposite effects on adenylate cyclase the receptors have distinct structure activity relationships for certain adenosine analogues. At A1-receptors the potency order is N6-R-phenylisopropyladenosine (R-PIA) ≥ S’-N-ethylcarboxamideadenosine (NECA) > S-PIA, whereas at A2-receptors it is NECA > R-PIA ≥ S-PIA (c.f. Stone 1985, Wiklund et al. 1989b). Stimulation or inhibition of adenylate cyclase is no longer regarded as a safe criterion for receptor type (Stone 1985). A further subdivision of A2 receptors into A2a and A2b was proposed, where A2a is a high affinity receptor (EC50 nanomolar range) and A2b is a low affinity receptor (EC50 micromolar range)(c.f. Bruns et al. 1987). Studies are at hand, suggesting adenosine receptors with agonist profiles that do not fit the definition of A1 and A2 receptors and a new class of adenosine receptors has been suggested: A3 (Ribeiro & Sebastiao 1986). We have previously reported a difference in structure activity relationships between adenosine A1 receptors at autonomic nerves versus those characterized e.g. in the CNS (Gustafsson et al. 1985, 1989, Wiklund et al. 1989a). The present study delineates presynaptic P1 receptors in the autonomic postganglionic nerves as clearly of A1 type, and probably constituting a novel subclass, A1b.