Demonstration of intrathecal and systemic morphine and ST-91 effects on fed canine upper gut motility.
We studied the effects of opioid and adrenergic agonists and antagonists given systemically intravenously and intrathecally on postprandial antral and small bowel motility in a chronic conscious dog model. We studied eight dogs with a surgically implanted thoracic spinal intrathecal injection catheter, and six gastrointestinal manometric perfusion catheters. Morphine given intrathecally or intravenously induced propagated clusters of intestinal pressure activity in the fed dogs. The minimal effective dose for morphine was 150 micrograms/kg by the intrathecal route and 450 micrograms/kg by the intravenous route. ST-91 (an alpha 2-adrenergic agonist) profoundly inhibited antral and small intestinal pressure activity with similar minimal effective dose (100 micrograms/kg) and duration of effect for both intravenous and intrathecal routes. Neither naloxone (3000 micrograms/kg) nor combined phentolamine (1500 micrograms/kg) with propranolol (300 micrograms/kg) altered postprandial antral or small intestinal motility. The capacity of pharmacologic agents to block morphine-induced activity fronts when administered in the same compartment (intravenously or intrathecally) was investigated. The minimally effective morphine-antagonist dose for naloxone was similar intrathecally and intravenously (36 micrograms/kg for both routes). ST-91 (100 micrograms/kg) when given intrathecally or intravenously blocked morphine-induced clustered phasic pressure activity while simultaneously abolishing postprandial small intestine phasic pressure activity. These data suggest the presence of opioid and alpha 2-adrenergic receptors in the spinal cord that can modulate gastrointestinal motility in the postprandial state. Pharmacological interactions between these systems occur at spinal and target organ levels.
Thomforde
G M
GM
Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Malagelada
J R
JR
Camilleri
M
M
Yaksh
T L
TL
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004435:Eating / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D009270:Naloxone; C011266:ST 91; D009020:Morphine; D011433:Propranolol; D003000:Clonidine; D010646:Phentolamine