Central and peripheral control of gastrointestinal and colonic motility by endogenous opiates in conscious dogs

The effects of two enkephalin analogues, (D-Ala2, Met5) and (D-Ala2, D-Leu5) enkephalinamide, on gastrointestinal and colonic motility were investigated in conscious fasted and fed dogs using chronically implanted strain gauges. The drugs, abbreviated here with the names DALAMIDE and DADLE, respectively, were administered by using both the intracerebroventricular and intravenous routes at increasing doses. In fasted dogs when administered via the intracerebroventricular route at a dose of 20 ng X kg-1, DALAMIDE disrupted the migrating myoelectric complex pattern. A similar effect was obtained only with a dose 25 times higher (500 ng X kg-1) administered intravenously; at this dosage DALAMIDE administered intravenously also reduced the colonic motility index by 66%. When intracerebroventricularly administered in fed dogs, 2 h after a meal, DALAMIDE (20 ng X kg-1) inhibited gastric motility but restored the jejunal migrating myoelectric complex pattern as "ectopic" complexes for 4-6 h. This effect however was not reproduced by intravenous treatment even at the highest dose used (500 ng X kg-1). Both intracerebroventricular and intravenous administration of DADLE, at doses as high as 100 and 500 ng X kg-1, respectively, affected neither the motility pattern nor the motility index of the antrum and proximal jejunum in the fasted or fed state. However, intracerebroventricular, but not intravenous, administration produced a short (10-15 min) increase of colonic motility. These results suggest that (a) Met-enkephalin influences the gastrointestinal motility predominately by a central action, manifested as a migrating myoelectric complex "reorganizing" effect in fed dogs; (b) Leu-enkephalin exerts a predominately centrally mediated stimulation of colonic motility, whereas Met-enkephalin inhibits it probably by a peripheral mechanism.