Noninvasive assessment of gastric emptying by near-infrared fluorescence reflectance imaging in mice: pharmacological validation with tegaserod, cisapride, and clonidine.
Noninvasive near-infrared fluorescence reflectance imaging (FRI) is an in vivo technique to assess physiological and molecular processes in the intact organism. Here we describe a method to assess gastric emptying in mice. TentaGel beads with covalently bound cyanine dye (Cy5.5) conjugates as fluorescent probe were administered by oral gavage. The amount of intragastric beads/label was derived from the fluorescence signal intensity measured in a region of interest corresponding to the mouse stomach. The FRI signal intensity decreased as a function of time reflecting gastric emptying. In control mice, the gastric half-emptying time was in agreement with literature data. Pharmacological modulation of gastric motility allowed the evaluation of the sensitivity of the FRI-based method. Gastric emptying was either stimulated or inhibited by treatment with the 5-HT(4) receptor agonists tegaserod (Zelnorm) and cisapride or the alpha(2)-receptor agonist clonidine, respectively. Tegaserod and cisapride dose-dependently accelerated gastric emptying. In contrast, clonidine dose-dependently delayed gastric emptying. In conclusion, FRI using fluorescently labeled beads allows the reliable determination of gastric emptying as well as the assessment of pharmacological interventions. The technique thus offers the potential to characterize molecular targets and pathways involved in physiological regulation and pharmacological modulation of gastric emptying.
Gremlich
Hans-Ulrich
HU
Novartis Institutes for BioMedical Research, Novartis Pharma AG, WSJ-386.14.48, CH-4002 Basel, Switzerland. hansulrich.gremlich@pharma.novartis.com
Martínez
Vicente
V
Kneuer
Rainer
R
Kinzy
Willy
W
Weber
Eckhard
E
Pfannkuche
Hans-Juergen
HJ
Rudin
Markus
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage; D020117:Cisapride / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000008:administration & dosage; D005746:Gastric Emptying / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D007211:Indoles; D017366:Serotonin Receptor Agonists; C105050:tegaserod; D003000:Clonidine; D020117:Cisapride