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 A3类腺苷受体对腺苷酸环化酶有抑制作用， 而A2类对腺苷酸环化酶具有刺激性。的子类 也存在腺苷受体。其中一些是抑制钙 通道，有些是刺激钾通道，有些激活 鸟苷酸环化酶，一些调节磷脂周转，一些引起 平滑肌松弛合成了另外的吡唑并吡啶， 分析A1和A2腺苷受体的拮抗剂活性， 对地西泮与GABAA受体结合的影响。大多数是非选择性的， A1受体选择性拮抗剂。某些吡唑并吡啶是 在刺激安定结合方面非常有效，因此可能具有 抗焦虑活性。其他仅表现出抑制活性 安定结合腺调节素，一种来自海利德蛙的两亲性肽 激动剂与Gi-蛋白偶联受体的刺激结合显然 由于受体-G-蛋白复合物转化为高亲和力 鸟苷酸游离状态。来自海利德蛙的同源肽 抑制激动剂的结合，正在研究中。慢性 咖啡因或茶碱的摄入改变了各种中枢神经系统的水平， 受体。只有β-肾上腺素能受体和烟碱受体似乎是 下调，提示黄嘌呤诱导的去甲肾上腺素增加 和乙酰胆碱周转。慢性可可碱，一种很弱的腺苷 受体拮抗剂和慢性异丁基甲基黄嘌呤，一种有效的 腺苷受体拮抗剂，以及一种有效的磷酸二酯酶 抑制剂，引起的，如咖啡因/茶碱，上调A1- 腺苷受体，但没有改变其他受体的水平。 对各种受体激动剂/拮抗剂的行为反应发生改变 咖啡因后，与观察到的受体水平的变化相一致。

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. Further pyrazolopyridine were synthesized and analyzed for antagonist activity at A1 and A2 adenosine receptors and for effects on diazepam-binding to GABAA receptors. Most were nonselective or were A1 receptor selective antagonists. Certain pyrazolopyridines were very potent in stimulating diazepam-binding and might therefore have anxiolytic activity. Others showed only inhibitory activity towards diazepam-binding. Adenoregulin, an amphophilic peptide from a hylid frog stimulated binding of agonists to Gi-protein-coupled receptors apparently due to conversion of the receptor-G-protein complex to a high affinity guanylnucleotide free state. Congeneric peptides from the hylid frog inhibited binding of agonists and are under investigation. Chronic caffeine or theophylline ingestion altered levels of a variety of central receptors. Only beta-adrenergic and nicotinic receptors appeared to be downregulated, suggestive of xanthine-induced increases in norepinephrine and acetylcholine turnover. Chronic theobromine, a very weak adenosine receptor antagonist, and chronic isobutylmethylxanthine, a potent adenosine receptor antagonist and, in addition, a potent phosphodiesterase inhibitor, caused, like caffeine/theophylline, upregulation of A1- adenosine receptors, but did not alter levels to other receptors. Behavioral responses to various receptor agonists/antagonists were altered after caffeine, consonant with observed changes in receptor levels.