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2.
J Parasitol ; 94(4): 771-9, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18576774

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.


Subject(s)
Cyclic GMP/physiology , Hymenolepis diminuta/metabolism , Ileum/metabolism , Animals , Colchicine/pharmacology , Cyclic GMP/antagonists & inhibitors , Cyclic GMP/metabolism , Cyclooxygenase Inhibitors/pharmacology , Hymenolepis diminuta/drug effects , Ileum/parasitology , Immunohistochemistry , Male , Niflumic Acid/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Purinones/pharmacology , Rats , Rats, Sprague-Dawley , Tubulin Modulators/pharmacology
3.
Int J Exp Pathol ; 89(6): 458-65, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19134055

ABSTRACT

The neurotrophin, glial-derived neurotrophic factor (GDNF), is essential for the development of the enteric nervous system (ENS) in both the embryo and neonate and may be important for maintenance and plasticity of ENS. The tapeworm, Hymenolepis diminuta, altered the number of cells containing GNDF in the host's jejunum and ileum. Numbers and locations of GDNF-containing cells were determined by applying monoclonal anti-GDNF antibody to intestinal segments collected from infected and uninfected age-matched rats during the initial 34 days post-infection (dpi). Most cells staining positive for GDNF were present in the lamina propria of the jejunum and ileum from both infected and uninfected rats. The co-localization of staining by the antibodies, anti-GDNF and anti-ED2 (a nuclear specific antibody for resident macrophages) indicated that at least 74% of the cells staining for GDNF were macrophages. Mast cells did not stain with the anti-GDNF antibody. The increased number of GDNF+ cells in the infected rat intestine suggests that this neurotrophin may play a role in the neural and mucosal responses to lumenal tapeworm infection.


Subject(s)
Cestode Infections/metabolism , Glial Cell Line-Derived Neurotrophic Factor/analysis , Hymenolepis diminuta , Intestine, Small/metabolism , Animals , Biomarkers/analysis , Cell Count , Cestode Infections/immunology , Ileum/chemistry , Ileum/immunology , Ileum/metabolism , Immunohistochemistry , Intestine, Small/chemistry , Intestine, Small/immunology , Jejunum/chemistry , Jejunum/immunology , Jejunum/metabolism , Macrophages/chemistry , Macrophages/metabolism , Male , Mast Cells/chemistry , Mast Cells/metabolism , Models, Animal , Rats , Rats, Sprague-Dawley
4.
Comp Biochem Physiol A Mol Integr Physiol ; 136(3): 591-603, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14613787

ABSTRACT

Serotonin (5-hydroxytryptamine, 5-HT) is an endogenous signalling molecule capable of altering small intestinal motility. Serotonin is normally present in the intestinal lumen and released by enterochromaffin cells of the mucosal epithelium. We found that intraduodenal infusion of exogenous serotonin causes a dose-dependent myoelectric response in the smooth muscle of the small intestine in the conscious rat. The response consists of repetitive bursts of action potentials (RBAP) that are characterized as short bursts of non-propagative myoelectric spiking. RBAP occur intermittently and only during the first 15 min after intralumenal serotonin infusion. After the initial 15 min period, the frequency of RBAP declines, and the myoelectric pattern shifts to prolonged and continuous spiking, eliminating the interdigestive migrating myoelectric pattern. The effects of intralumenal serotonin are not replicated by parenteral or intraperitoneal infusion nor by intralumenal infusion of 5-hydroxytryptophan or 5-hydroxyindoleacetic acid. The response to intralumenal serotonin was eliminated by several specific 5-HT receptor antagonists. On repeated intralumenal administration of serotonin, the RBAP response decreased demonstrating a decreased sensitivity of the muscle contraction on re-exposure to serotonin. We conclude that intralumenal infusion of serotonin can temporarily initiate specific small intestinal muscle events that are not generated by serotonin from other non-lumenal administration sites. We speculate that an afferent neuro-pathway is necessary for the induction of RBAP, since RBAP are not observed from in vitro muscle preparations.


Subject(s)
Action Potentials/drug effects , Duodenum/drug effects , Serotonin/pharmacology , Animals , Dose-Response Relationship, Drug , Duodenum/physiology , Male , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Rats , Rats, Sprague-Dawley , Receptors, Serotonin/metabolism , Serotonin/metabolism , Serotonin Antagonists/pharmacology
5.
J Parasitol ; 89(6): 1136-41, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14740900

ABSTRACT

Tapeworms alter the physiological environment of the host's small intestinal lumen by contracting the intestinal smooth muscle, thereby slowing the transit of intestinal contents. We hypothesize that parasite-to-host molecular signaling is responsible for the specific patterns of small intestinal smooth muscle contraction observed both during tapeworm infection and after the infusion of tapeworm-secreted molecules into the intestinal lumen of unanesthetized rats. Of the tapeworm-secreted compounds tested, only lumenal infusion of guanosine 3',5'-cyclic monophosphate (cGMP) induced contractile patterns that mimic those observed during tapeworm infection. The response to cGMP occurred in a concentration-dependent fashion. Our study clearly demonstrates that cGMP can serve as an extracellular signal molecule regulating small intestinal motility mechanisms in vivo.


Subject(s)
Cyclic GMP/physiology , GTP-Binding Protein Regulators/physiology , Hymenolepiasis/parasitology , Hymenolepis/physiology , Intestine, Small/physiology , Action Potentials , Animals , Biological Assay/methods , Cyclic GMP/metabolism , Electromyography , GTP-Binding Protein Regulators/metabolism , Gastrointestinal Motility/physiology , Host-Parasite Interactions , Hymenolepiasis/physiopathology , Intestine, Small/parasitology , Male , Muscle, Smooth/physiology , Rats
6.
J Parasitol ; 88(2): 227-31, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12053990

ABSTRACT

The rat tapeworm Hymenolepis diminuta alters the myoelectric activity of the small intestine. To determine if secreted factors from the tapeworm are responsible for these alterations of intestinal smooth muscle activity, tapeworm-conditioned medium (TCM) obtained from in vitro culture was infused via an indwelling cannula into the duodenum of an uninfected rat. Myoelectric recordings were analyzed for sustained spike potentials (SSP) and repetitive bursts of action potentials (RBAP), the previously characterized tapeworm modifications of the normal interdigestive myoelectric pattern. Results indicated that TCM initiated SSP, but not RBAP in the intestine of the uninfected rat. The SSP-inducing signal factor activity, present in TCM, was retained after boiling, prolonged freezing, proteinase treatment, and passage through a 10-kDa exclusion filter. The signal factor was soluble in the aqueous phase on lipid extraction. It was concluded that the SSP-inducing signal factor is a nonproteinaceous, heat-resistant, low-molecular weight, water soluble molecule.


Subject(s)
Duodenum/physiology , Hymenolepis/physiology , Muscle Contraction/physiology , Muscle, Smooth/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Culture Media, Conditioned , Duodenum/drug effects , Electromyography , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Rats , Rats, Sprague-Dawley
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