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BACKGROUND & PURPOSE Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound ('MuDelta'), could(More)
BACKGROUND Subsets of myenteric neurons have been identified. To determine the proportional representation of neurons in each, it is necessary to relate the number of neurons in the subset to that of the complete set. Prior estimates of total numbers of neurons, obtained with many different markers, have varied widely. METHODS Markers were compared for(More)
The peristaltic reflex can be evoked in the absence of input from the CNS because the responsible neural pathways are intrinsic to the intestine. Mucosal enterochromaffin cells have been postulated to be pressure transducers, which activate the intrinsic sensory neurons that initiate the reflex by secreting 5-HT. All of the criteria necessary to establish(More)
Oil of mustard (OM) is a potent neuronal activator that promotes allodynia and hyperalgesia within minutes of application. In this study, OM was used to induce an acute colitis. We also investigated whether intracolonic OM-induced inflammation alters gastrointestinal (GI) function over a longer time frame as a model of postinflammatory irritable bowel(More)
Megacolon occurs in neonatal and adult transgenic mice that overexpress the Hoxa-4 gene. Abnormalities, which are restricted to the terminal colon of these mice, include a hypoganglionosis, abnormal enteric ganglia with a structure appropriate for extra-enteric peripheral nerve and not the enteric nervous system (ENS), and gaps in the longitudinal muscle(More)
A small set of acyclic analogs 5 were prepared to explore their structure-activity relationships (SARs) relative to heterocyclic core, opioid receptor (OR) agonists 4. Compound 5l was found to have very favorable OR binding affinities at the δ and μ ORs (r K(i) δ=1.3 nM; r K(i) μ=0.9 nM; h K(i) μ=1.7 nM), with less affinity for the κ OR (gp K(i) κ=55 nM).(More)
  • Paul R Wade
  • 2002
As we enter the 21st century, the segment of the population that is the most rapidly expanding is that comprised of individuals 85 yr of age and older. Dysfunctions of the gastrointestinal (GI) system, including dysphagia, constipation, diarrhea, and irritable bowel syndrome are more common complaints of the elderly, yet our knowledge of the aging GI tract(More)
A 2-year-old spayed female Siamese cat was presented with clinical liver disease characterized by anorexia; depression; elevations in serum levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase; hyperbilirubinemia; and icterus. Liver biopsy diagnosed hepatocellular degeneration with marked centrilobular hepatocellular(More)
Intracellular recording was used in vitro to analyze electrophysiological properties of neurons in myenteric ganglia of guinea pig distal colon. The neurons were classified into six types based on their electrical behavior. Type 1 colonic neurons discharged action potentials throughout depolarizing current pulses and were otherwise similar to S/type 1(More)