Central-adenosine A₁ receptor involved in the thermal regulation effect of YZG-330, a N⁶-substituted adenosine derivative, in mice

Adenosine receptors (AR) play an important role in the regulation processes for body temperature and vigilance states. During our previous studies, we noticed that aminophylline (a non-selective, blood-brain- barrier penetrably AR antagonist) could attenuate the effects of YZG-330 (2R, 3S, 4R, 5R)-2-(hydroxymethyl)- 5-(6-(((R)-1-phenylpropyl)amino)-9H-purin-9-yl)tetrahydrofuran-3, 4-diol on lowering the body temperature. Hereby, we focused ourselves on the character of thermal regulation effect of YZG-330 in mice and tried to specify the receptor subtype via giving typical adenosine receptor antagonists. The results showed that both of the magnitude and lasting time of the effect that YZG-330 played on decreasing body temperature are in a dose-dependent manner: within the next 3 hour after intragastric administration (ig) of 0.25, 1 or 4 mg·kg^-1 YZG-330, the extreme values on body temperature decreasing were (1.2 ± 0.3) ℃, (3.6 ± 0.4) ℃ (P < 0.001) and (7.4 ± 0.5) ℃ (P < 0.001), separately; whereas the duration that body temperature below 34 ℃ were 0, (10 ± 5) and (153 ± 4) min, separately. Adenosine A₁ receptor (A₁R) antagonist (DPCPX) could effectively reverse YZG-330's effect on decreasing body temperature, with intraperitoneal administration of DPCPX (5 mg·kg^-1) 20 min prior than YZG-330 (4 mg·kg^-1, ig), the extreme value on body temperature decreasing was (3.5 ± 0.7) ℃ (P < 0.001), the duration that body temperature below 34 ℃ was (8 ± 6) min (P < 0.001). However, adenosine A_2a receptor antagonist, SCH-58261, did not show any influence on the effects of YZG-330 at all. Combined with the fact that 8-SPT (a non-selective, blood-brain-barrier impenetrably AR antagonist) did not reverse the effect of YZG-330, we come to the conclusion that central-adenosine A₁ receptor plays a significant role on the thermal regulation effect of YZG-330.