The effect of alpha-1-adrenoreceptor agonist and antagonist administration on human upper gastrointestinal transit and motility.
To explore the role of alpha-1-adrenoreceptor-mediated pathways on human upper gut motor function in vivo, we studied the effects of the alpha-1-agonist phenylephrine and the alpha-1-antagonist thymoxamine on oro-caecal transit and antroduodenal motor activity. Transit was measured using a standard exhaled-breath hydrogen method, and motility was measured by intraluminal manometry. Oro-caecal transit was unaffected by 80 mg thymoxamine [median 63 min (range 35-164 min) vs. control, 65 min (range 30-155 min), P greater than 0.1]. However, phenylephrine (2.4 micrograms/kg/min) consistently delayed oro-caecal transit time to 103 min (50-215 min), P greater than 0.005. Co-administration of thymoxamine abolished this phenylephrine-induced delay. The mean amplitude of antral postprandial contractions was reduced by phenylephrine from 29 (13-37) to 10 (3-13) mmHg (P less than 0.02). In contrast, neither the pattern nor the mean inter-contraction interval was altered. Responses to phenylephrine in the duodenum were similar to those in the antrum, with reduction in amplitude from 12 (3-18) to 6 (5-13) mmHg without alteration in the pattern or interval between contractions. Nutrient transit through the upper gut can thus be inhibited via activation of an alpha-1-adrenoreceptor-mediated pathway. Failure of alpha-1-antagonist administration to alter oro-caecal transit suggests that this pathway is not tonically active, and it is therefore unlikely to play a major role in nutrient passage under normal circumstances.
Department of Medicine, Oldchurch Hospital, Romford, London, UK.
A S
AS
McIntyre
D G
DG
Thompson
W R
WR
Burnham
E
E
Walker
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D002432:Cecum / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004386:Duodenum / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D013948:Moxisylyte / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D013948:Moxisylyte