ADENOSINE RECEPTOR AGONISTS AND ANTAGONISTS

腺苷通过调节多种生理功能， 与至少两种主要类型的腺苷受体相互作用。 的 A1和A3类腺苷受体对腺苷酸具有抑制作用 环化酶，而A2类是刺激腺苷酸环化酶。 腺苷受体的亚类也存在。 其中一些是 抑制钙通道，有些对钾通道有刺激作用 通道，一些激活鸟苷酸环化酶，一些调节磷脂 翻转和一些引起平滑肌松弛。 一系列 合成了吡唑并吡啶。 乙基1-乙基-4- 丁基氨基吡唑并吡啶-5-甲酸酯是非特异性的A1-和A2 a- 腺苷受体拮抗剂的效力约50倍， 茶碱 Adenoregulin，一种从亚马逊海蛞蝓中分离的肽 青蛙和黄蜂肽mastoparan都能显著刺激 A1、α-2和5-HT 1A受体激动剂。 所有这些受体都是 通过Gi类蛋白与腺苷酸环化酶偶联。 腺调节素 和mastoparan增强Gi蛋白处鸟苷酸的周转。 它 似乎通过这些增强激动剂与受体的结合， 肽是由于受体-G-蛋白复合物转化为 高亲和力无鸟苷酸状态。 没有直接证据 腺调节素或乳蛋白聚糖对磷脂酶C的功能性激活 得出 相反，这些肽对磷酸肌醇具有抑制作用， 透化细胞中的分解。 小鼠的慢性咖啡因摄入 导致A1-腺苷、5-羟色胺、胆碱能和 GABAA受体和L-型钙通道和β- 肾上腺素能受体 A2 a-腺苷、α-肾上腺素能、多巴胺能和 NMDA受体未发生改变。 腺苷的行为反应 类似物，咖啡因，胆碱能和多巴胺能药物在 慢性咖啡因 乙醇的行为学效应是 在慢性咖啡因后明显下降。

Adenosine regulates a wide range of physiological functions through interaction with at least two major classes of adenosine receptors. The A1 and A3 classes of adenosine receptors are inhibitory to adenylate cyclase, while the A2 class is stimulatory to adenylate cyclase. Subclasses of adenosine receptors also occur. Some of these are inhibitory to calcium channels, some are stimulatory to potassium channels, some activate guanylate cyclase, some modulate phospholipid turn-over and some cause smooth muscle relaxation. A series of pyrazolopyridines were synthesized. The ethyl 1-ethyl-4- butylaminopyrazolopyridine-5-carboxylate was a non-specific A1- and A2a- adenosine receptor antagonist with a potency some 50-fold greater than theophylline. Adenoregulin, a peptide isolated from an Amazonian hylid frog and mastoparan, a wasp peptide, both markedly stimulate binding of agonists to A1, alpha-2 and 5-HT1A receptors. All of these receptors are coupled via Gi-class proteins to adenylate cyclase. Both adenoregulin and mastoparan enhance turnover of guanylnucleotides at Gi proteins. It appears that enhancement of binding of agonists to receptors by these peptides is due to conversion of the receptor-G-protein complex to a high-affinity guanyl nucleotide-free state. No evidence for direct functional activation of phospholipase C by adenoregulin or mastoparan was obtained. Instead, the peptides were inhibitory to phosphoinositide breakdown in permeabilized cells. Chronic caffeine ingestion by mice causes increases in density of A1-adenosine, serotonin, cholinergic and GABAA-receptors and L-type calcium channels and decreases in beta- adrenergic receptors. A2a-Adenosine, alpha-adrenergic, dopaminergic and NMDA receptors appear unaltered. Behavioral responses to adenosine analogs, caffeine, cholinergic and dopaminergic agents are altered after chronic caffeine. The behavioral depressant effects of ethanol are markedly decreased after chronic caffeine.