Different endogenous opioid effects on delta- and mu-receptor subtypes in antral and duodenal motility of conscious dogs.
To evaluate the role of endogenous opioids in regulation of upper gastrointestinal motility in unanesthetized dogs and to differentiate the actions on mu- and delta-opioid receptors, seven strain gauges and five platinum electrodes were chronically implanted at the serosa along the antrum and duodenum and connected to a plug in the neck of the dog. Signals were processed by a Hellige AC amplifier, a rectilinear recorder, and a data aquisition system. A motility index (MI) was calculated and together with the electrical data a contractile activity percentage (CAP) was determined for consecutive 30 min periods. The delta-opioid antagonist ICI 741 864 and the mu-receptor blocker naloxone were injected intraarterially through a chronic Groshong catheter placed in the pyloric region and connected to a subcutaneous port. After a meal of solid food, ICI 174 864 increased motility relative to controls in the antrum averaged over 5 hr by 144.4%+/-26 for the MI and 73%+/-26 for CAP; after naloxone MI increased by 222%+/-60 and CAP 121%+/-76. In the duodenum, ICI 174 864 decreased MI over a range of 57% to 22% (P < 0.05). Naloxone increased MI and CAP significantly after 2.5 hr. We interpreted the results of ICI 174 864 in the duodenum to reflect suppression of a tonic opioid influence at the delta-receptor mainly at the prevertebral ganglion. In the interdigestive state in 56% of the dogs, naloxone delayed the occurrence of phase III of the migrating myoelectric complex (MMC) for up to 370 min, while under ICI 174 864, normal interdigestive cycles were present. Disturbance of the timing of the interdigestive cycles at central mu-opioid receptors may by involved in the effect.
Holle
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GE
Gastroenterological Research Laboratory, Walther Straub Institute for Pharmacology and Toxicology, Ludwig Maximilians University, Munich, Germany.
Steinbach
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D000818:Animals; D004285:Dogs; D004386:Duodenum / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000502:physiology*; D011706:Pyloric Antrum / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology*
D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone