A comparison of peripheral and central effects of clonidine on rat intestinal transit.
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.
Tadano
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Kisara
K
K
Stewart
J J
JJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003967:Diarrhea / Q000188:drug therapy; D004386:Duodenum / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation; D008297:Male; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D012277:Ricinoleic Acids / Q000008:administration & dosage; D014628:Vagotomy
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D012277:Ricinoleic Acids; C030521:ricinoleic acid; D003000:Clonidine