Tadano T, Kisara K, Stewart J J
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Res Commun Chem Pathol Pharmacol. 1992 Nov;78(2):161-79.
This study was designed to examine the effects of centrally or peripherally administered clonidine on small intestinal transit (SIT) in rats with diarrhea. Adult, male rats weighing 200 to 250 grams were surgically implanted with a silicone catheter in the proximal small intestine. Some animals were additionally implanted with a cannula in the right lateral cerebroventricle. SIT was determined by measuring the progression of an intraduodenally administered radioactive marker (Na2CrO4, 0.5uCi) along the small intestine. In most experiments, the effects of clonidine or saline were determined in animals challenged with sodium ricinoleate (100 mg) intraduodenally, the active ingredient in castor oil except treatment with reserpine. Given subcutaneously (s.c.) clonidine significantly inhibited SIT at doses between 25 and 200 micrograms/kg. The effects of s.c. clonidine were antagonized by yohimbine, but not by reserpine or subdiaphragmatic truncal vagotomy. In contrast, given intracerebroventricularly (i.c.v.) clonidine produced a more long lasting effect at total doses greater than 20 micrograms. Intestinal antipropulsive effects of i.c.v. clonidine were blocked by yohimbine, but not by prazosin. Reserpine (s.c.) or 6-hydroxydopamine (i.c.v.) did not affect the actions of central clonidine. However, effects of i.c.v. clonidine were abolished after vagotomy. The results indicate that clonidine inhibits rat intestinal transit in similar total doses when given s.c. or i.c.v. Inhibition of SIT by clonidine results from alpha-2 adrenergic receptor activation. In the case of i.c.v. clonidine, the receptors appear to be located postsynaptically and the response is dependent upon intact vagal innervation.
本研究旨在探讨中枢或外周给予可乐定对腹泻大鼠小肠转运（SIT）的影响。将体重200至250克的成年雄性大鼠通过手术在近端小肠植入硅胶导管。部分动物还在右侧侧脑室植入套管。通过测量十二指肠内给予的放射性标记物（Na2CrO4，0.5微居里）在小肠中的推进情况来测定SIT。在大多数实验中，在十二指肠内给予蓖麻油酸钠（100毫克，蓖麻油中的活性成分，除用利血平处理外）激发的动物中测定可乐定或生理盐水的作用。皮下注射（s.c.）可乐定在25至200微克/千克的剂量下可显著抑制SIT。皮下注射可乐定的作用可被育亨宾拮抗，但不能被利血平或膈下迷走神经切断术拮抗。相比之下，脑室内（i.c.v.）给予可乐定在总剂量大于20微克时产生更持久的作用。脑室内给予可乐定的肠道抗推进作用可被育亨宾阻断，但不能被哌唑嗪阻断。利血平（皮下注射）或6-羟基多巴胺（脑室内注射）不影响中枢可乐定的作用。然而，迷走神经切断术后脑室内给予可乐定的作用消失。结果表明，皮下或脑室内给予可乐定在相似的总剂量下均可抑制大鼠小肠转运。可乐定对SIT的抑制作用源于α-2肾上腺素能受体激活。就脑室内给予可乐定而言，受体似乎位于突触后，且反应依赖于完整的迷走神经支配。
