腺核苷是一個內生性嘌呤，在哺乳動物組織扮演釵h生理角色，被視為生理恆定作用的神經調節者，其作用主要經由腺核苷A1及A2接受體所調節。近年來研究發現在老鼠身上投與腺核苷衍生物，會產生運動活性降低、鎮靜及體溫降低之生理反應。先前我們實驗室研究發現，在白兔和大白鼠OVLT區域給予低頻率 (1-30 Hz) 電刺激能降低動物體溫。 並被事先OVLT投予非選擇性腺核苷接受體拮抗劑aminophylline (50 mg/2 ml) 所拮抗。本研究進一步結果顯示，OVLT區域直接投與A1接受體作用劑 (N6-p-sulfophenyladenosine; 20 mg/2 ml) 或A2接受體拮抗劑 (3,7-Dimethyl-1-propargylxanthine; 2 mg/2 ml) 可模擬此一低頻電刺激所引起的動物降溫作用。反之，aminophylline (50 mg/2 ml) 和A1接受體拮抗劑 (8-p-sulfophenyltheophylline; 20 mg/2 ml) 投與則引起動物升溫作用。為證實腺核苷OVLT區域對降溫機制調控的專一性，我們將同劑量的N6-p-sulfophenyladenosine靜脈注射，及投與下視丘區域，結果都無法使動物體溫降低。進一步實驗發現OVLT投與IL-1b (10 ng/2 ml) 引起之熱原性發燒，可明顯受N6-p-sulfophenyladenosine事前給藥所阻斷，但不受8-p-sulfophenyltheophylline前後給藥所影響，8-p-sulfophenyltheophylline (20 mg/2 ml) 引起的升溫作用也明顯受投與COX阻斷劑 (diclofenac; 50 mg/2 ml)所阻斷。綜合結果，OVLT區域腺核苷的釋出能經由A1接受體而達到體溫調降作用，而熱原性發燒機制中，部份可能藉由干擾腺核苷的釋出或阻斷A1接受體，增加前列腺素生合成而引起白兔發燒現象。 Adenosine is a nucleoside which has been shown to participate in the regulation of physiological activity in a variety of mammalian tissues, and has been recognized as a homeostatic neuromodulator. The actions of adenosine are mediated through the adenosine A1 and A2 receptors. Many studies showed that adenosine analogs produced a cluster of physiological effects which included reduced locomotor activity, sedation and hypothermia. Our laboratory unpublished data showed that low frequency electrical stimulation of OVLT caused a hypothermic effect, thet can be blocked by pretreating a non-selective adenosine receptor antagonist aminophylline (50 mg/2 ml). The effect of adenosine-induced hypothermia and pyrogenic fever in OVLT were investigated following intra-OVLT and intravenous (iv) injection in rabbits. By administering to the OVLT region, an A1 receptor agonist, N6-p-sulfophenyladenosine (20 mg/2 ml), and an A2 receptor antagonist, 3,7-Dimethyl-1-propargylxanthine (2 mg/2 ml), can mimic the hypothermic effect. In contrast, aminophylline (50 mg/2 ml) and an A1 receptor antagonist, 8-p-sulfophenyltheophylline (20 mg/2 ml), induced hyperthermic effect. In order to identify the specific effect to hypothermic modulation in OVLT region, the same dose of N6-p-sulfophenyladenosine was administered intravenously and intra-anterior hypothalamus, but caused no hypothermic response. Further investigation showed the interleukin-1b (10 ng/2 ml)-induced fever was attenuated by pretreating N6-p-sulfophenyladenosine (20 mg/2 ml) in the OVLT, but no affected by pre- or post-treatment of 8-p-sulfophenyltheophylline (20 mg/2 ml). The hyperthermic effect of 8-p-sulfophenyltheophylline administration was also blocked by a COX blocker (diclofenac; 50 mg/2 ml). Adenosine released in the OVLT region can exert the hypothermic effect through A1 receptor activation, the possible mechanism of pyrogenic fever in rabbits may involve with increasing prostaglandin production via interference of adenosine release
