title: cGMP secreted from the tapeworm Hymenolepis diminuta is a signal molecule to the host intestine.
abstract: 3',5'-Cyclic guanosine monophosphate (cGMP), a well-known intracellular second messenger, is released to the intestinal lumen by the tapeworm, Hymenolepis diminuta. Enzyme-linked immunosorbent assay analysis of tapeworm conditioned media shows that cGMP is released at a constant rate. Multidrug resistant (MDR) proteins are efflux transporters for cyclic nucleotides. Two MDR inhibitors, niflumic acid and zaprinast, inhibit cGMP secretion by tapeworms and change the cGMP localization within the tapeworm tegument, as assessed by immunochemistry. cGMP, normally present throughout the tapeworm tegumental cytoplasm, is absent from the outer cytoplasmic band upon treatment with inhibitors. Inhibition of cGMP secretion by colchicine indicates that cGMP secretion is cytoskeleton dependent. Binding studies of [3H]cGMP to ileal segments of intestine demonstrate 2 saturable, reversible, and high-affinity binding sites. These studies demonstrate that cGMP is secreted from the cestode via a cytoskeleton-dependent mechanism and MDR efflux transporters. In addition, cGMP reaching the intestinal lumen can bind to the mucosa via receptors for cGMP. These data, combined with earlier observations of cGMP altering intestinal motility and slowing lumenal transit, indicate that tapeworms alter the physiology of the host digestive process via the secretion and binding of extracellular cGMP to lumenal receptors in the host intestine.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. nzimmer@mcw.edu
authors.forename: Noah P
authors.initials: NP
authors.lastname: Zimmerman
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brownfield
authors.forename: Jan
authors.initials: J
authors.lastname: DeVente
authors.forename: Paul
authors.initials: P
authors.lastname: Bass
authors.forename: John A
authors.initials: JA
authors.lastname: Oaks
mesh_terms: D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D048190:Hymenolepis diminuta / Q000187:drug effects / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism* / Q000469:parasitology; D007150:Immunohistochemistry; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D050257:Tubulin Modulators; D009544:Niflumic Acid; C011145:zaprinast; D006152:Cyclic GMP; D003078:Colchicine