MODULATION OF HUMAN UPPER INTESTINAL NUTRIENT TRANSIT BY A BETA-ADRENOCEPTOR MEDIATED PATHWAY

To explore the role played by beta adrenoreceptor mediated pathways on human upper gut function a series of studies were conducted into the effects of beta adrenoreceptor agonists and antagonists on orocaecal and duodenocaecal transit and on antral and duodenal motor activity. Under control conditions orocaecal transit was consistent within individuals (mean coefficient of variation (18.0%) but varied widely between individuals (median transit 63 minutes, range 33-164). Prior administration of the non-selective beta adrenergic antagonist propranolol consistently hastened orocaecal transit (median transit 51:25-93, v control p<0.005). The selective beta-1 antagonist, atenolol, also hastened transit (median transit 50:35-93 minutes, v control p<0.01). The magnitude of an individual's response to beta blockade correlated closely with the orocaecal transit (Tau=0.54, p<0.01). Duodenocaecal transit was also hastened by propranolol from control values of 66:45-107 minutes to 50:16-62 minutes, p<0.025). In contrast neither duodenal nor antral motility were consistently altered by beta blockade. The beta adrenoreceptor agonist, isoprenaline, delayed both orocaecal transient (97:55-178 minutes, v control p<0.005) and also duodenocaecal transit (160:45-215 minutes, v 73:40-133) (p<0.025). Isoprenaline also reduced antral motility by an effect which appeared to occur predominantly through a reduction in contraction amplitude (from a median amplitude of 27:5.39 mm Hg to 14:3-24 mm Hg, p<0.03) rather than an effect on the interval between contractions. No effect on either amplitude or frequency of duodenal motor activity was observed. A beta adrenoreceptor mediated pathway thus appears to exert a biologically relevant effect on gut function not only under conditions of sympathetic stimulation, but also at rest when a basal beta adrenergic tone appears to influence the speed of nutrient transit through the human upper gut.