title: Comparative effects of ketanserin, atropine and methysergide on the gastrointestinal effects of hyperserotoninemia in the awake dog.
abstract: Intestinal handling of water and electrolytes and motility were monitored in conscious dogs with chronic 25-cm Thiry-Vella loops of proximal jejunum. Absorption/secretion was quantitated using a neutral isosmotic perfusate containing [14C]polyethylene glycol as a recovery marker. Under basal conditions the animals absorbed water, Na+ and Cl-, while there was no net action on K+. Intravenous serotonin infusion (30 micrograms/kg/min) increased circulating levels of serotonin to a mean of 1556 +/- 191 ng/ml within 15 min of the commencement of the infusion. The infusion induced a significant secretion of water (mean -73 +/- 7 microliters/min) and electrolytes (sodium -10.4 +/- 0.7 muEq/min; potassium -0.8 +/- 0.05 muEq/min; chloride -12.4 +/- 1.0 muEq/min) in the dogs and all showed signs of hyperserotoninemia (salivation, loose bowel movements, tachypnea). After administration of ketanserin (33 micrograms/kg/min), a significant reduction in secretion was demonstrated (water +20.8 +/- 16.1 microliters/min; sodium 7.2 +/- 3.0 muEq/min; potassium -0.02 +/- 0.1 muEq/min; and chloride -1.9 +/- 2.8 muEq/min) as well as reduced motor activity. A similar antisecretory effect was demonstrated with atropine infusion (20 micrograms/kg/min), although this drug had a far more significant effect on the gastrointestinal motility recorded in the loop. Infusion of methysergide (33 micrograms/kg/min) did not significantly affect secretion (water -111.4 +/- 59.0 microliter/min; sodium -17.4 +/- 9 muEq/min; potassium -0.9 +/- 0.4 muEq/min; chloride -20.3 +/- 7.0 muEq/min). These results suggest possible actions which may make ketanserin useful in the treatment of symptoms of the carcinoid syndrome.
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D005769:Gastrointestinal Motility / Q000187:drug effects; D007650:Ketanserin; D008784:Methysergide / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000097:blood* / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D010880:Piperidines; D011985:Receptors, Serotonin; D012701:Serotonin; D001285:Atropine; D007650:Ketanserin; D008784:Methysergide