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类腺苷受体对腺苷酸环化酶有抑制作用， A2类对腺苷酸环化酶有刺激作用。 腺苷亚类 受体也会出现。 其中一些是抑制钙通道， 有些刺激钾通道，有些激活鸟苷酸 环化酶，有些调节磷脂，翻转，有些导致光滑 肌肉松弛通过一个不明确的机制。 的活动 一系列的2-取代腺苷导致模型的发展， A2 A-腺苷受体上的结合位点。 这是一个疏水的 与腺嘌呤环的2位分开的位点， 横向公差小。 与A2 A受体的亲和力相关性良好 作为血管扩张剂的效力。 抑制或刺激 在一种亚马逊水螅的分泌物中发现了激动剂的结合 青蛙 刺激肽腺调节素具有以下序列 GLWSKIKEVGKEAAAKAAAKAAGKAALGAVSEAV。 很可能是一个或多个D- 存在氨基酸残基。 NIH品系雄性大鼠的慢性咖啡因 白色小鼠导致自发探索活动减少。 的 咖啡因刺激自发活动的阈值降低， 是腺苷类似物抑制效应的阈值。 的 尼古丁的副作用被消除，而毒蕈碱的副作用 激动剂，oxotremorine略有减少。 因此，慢性咖啡因 似乎显著改变了中央腺苷的功能， 胆碱能通路

Adenosine regulates a wide range of physiological functions through interaction with at least two major classes of adenosine receptors. The A1 class of adenosine receptors is 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 through a poorly defined mechanism. Activities of a range of 2-substituted adenosines led to development of model for the binding site on A2A-adenosine receptors. This consisted of a hydrophobic site separated from the 2-position of the adenine ring by a region with little lateral tolerance. Affinities at A2A-receptors correlated well with potencies as vasodilators. Peptides inhibitory or stimulatory to binding of agonists were discovered in secretions from an Amazonian hylid frog. The stimulatory peptide adenoregulin had the following sequence GLWSKIKEVGKEAAKAAAKAAGKAALGAVSEAV. It appears likely that one or more D- amino acid residues are present. Chronic caffeine in NIH strain male white mice results in a reduction in locomotor exploratory activity. The threshold for stimulation of locomotor activity to caffeine is lowered as are the thresholds for depressant effects of adenosine analogs. The depressant effects of nicotine are abolished, while those of a muscarinic agonist, oxotremorine are slightly reduced. Thus, chronic caffeine appears to significantly alter function of central adenosine and cholinergic pathways.