Clonidine and lidamidine (WHR-1142) stimulate sodium and chloride absorption in the rabbit intestine.
The effects of clonidine and lidamidine on ion transport in the intestine of the rabbit were determined. In the ileum both clonidine (10(-6) M) and lidamidine (10(-3) M) (a) decreased the short circuit current (-1.9 +/- 0.3 and -2.0 +/- 0.4 muEq/h . cm2, respectively) and potential difference; (b) increased net sodium absorption (2.0 +/- 0.6 and 1.8 +/- 0.4 muEq/h . cm2) and chloride absorption (3.4 +/- 0.5 and 3.4 +/- 0.6 muEq/h . cm2); and (c) increased tissue conductance (8.7 +/- 1.7 and 10.0 +/- 1.6 mmho/cm2). The increase in net sodium and chloride absorption was primarily due to an increase in mucosal-to-serosal movement of the ions and a decrease in serosal-to-mucosal movement of chloride. The action of clonidine on the short circuit current was quantitatively similar to the action of epinephrine. Both were readily reversed by yohimbine, a specific alpha 2-adrenergic antagonist. Further, methoxamine, an alpha 1-adrenergic agonist has no effect on the short circuit current up to the concentration of 10(-5) M; and prazosin, an alpha 1-adrenergic antagonist, did not affect the change of the short circuit current induced by epinephrine. The results indicate the presence of alpha 2-adrenergic receptors on the intestine and suggest that alpha 2-adrenergic stimulation may account for the effect of epinephrine on ion transport. Lidamidine was studied because it is structurally related to clonidine and has many similar actions. Yohimbine transiently reversed the effect of lidamidine. alpha 1-Adrenergic or dopaminergic antagonists did not reverse the effect of lidamidine, suggesting that it may affect alpha 2-adrenergic receptors. The results indicate that both clonidine and lidamidine stimulate electrolyte absorption and may be clinically useful.
D000200:Action Potentials; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D007082:Ileum / Q000502:physiology; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D010671:Phenylurea Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000930:Antidiarrheals; D002712:Chlorides; D010671:Phenylurea Compounds; D012964:Sodium; D003000:Clonidine; C020918:lidamidine