Original Articles

Effects of adenosine agonist R-phenylisopropyl-adenosine on halothane anesthesia and antinociception in rats

Hai-chun MA, Yan-fen WANG, Chun-sheng FENG, Hua ZHAO, Shuji DOHI


Aim: To investigate the antinociceptive effect of adenosine agonist Rphenylisopropyl-
adenosine (R-PIA) given to conscious rats by intracerebroventricular
(ICV) and intrathecal (IT), and identify the effect of R-PIA on minimum
alveolar concentration (MAC) of halothane with pretreatment of A1receptor antagonist
8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or K+ channel blocker
4-aminopyridine (4-AP). Methods: Sprague-Dawley rats were implanted with 24-
gauge stainless steel guide cannula using stereotaxic apparatus and ICV method,
and an IT catheter (PE-10, 8.5 cm) was inserted into the lumbar subarachnoid
space, while the rats were under pentobarbital anesthesia. After one week of
recovery from surgery, rats were randomly assigned to one of the following
protocols: MAC of halothane, or tail-flick latency. All measurements were performed
after R-PIA (0.8–2.0 μg) microinjection into ICV and IT with or without
pretreatment of DPCPX or 4-AP. Results: Microinjection of adenosine agonist RPIA
in doses of 0.8–2.0 μg into ICV and IT produced a significant dose- and timedependent
antinociceptive action as reflected by increasing latency times and
ICV administration of adenosine agonist R-PIA (0.8 μg) reducing halothane anesthetic
requirements (by 29%). The antinociception and reducing halothane requirements
effected by adenosine agonist R-PIA was abolished by DPCPX and
4-AP. Conclusion: ICV and IT administration of adenosine agonist R-PIA produced
an antinociceptive effect in a dose-dependent manner and decreased halothane
MAC with painful stimulation through activation of A1 receptor subtype,
and the underlying mechanism involves K+ channel activation.