cyclic-gmp and Hymenolepiasis

Topics: Action Potentials; Animals; Cyclic GMP; Dose-Response Relationship, Drug; Gastrointestinal Motility; Hymenolepiasis; Hymenolepis diminuta; Muscle, Smooth; Rats; Succinic Acid

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.

Topics: Action Potentials; Animals; Biological Assay; Cyclic GMP; Electromyography; Gastrointestinal Motility; GTP-Binding Protein Regulators; Host-Parasite Interactions; Hymenolepiasis; Hymenolepis; Intestine, Small; Male; Muscle, Smooth; Rats

During in vitro incubation, Hymenolepsis diminuta secretes substances into the medium that inhibit DNA synthesis in the germinative region of freshly isolated, uncrowded worms. Of the many substances that are released by H. diminuta into the medium, earlier studies indicate that only succinate, acetate, glucosaminic acid, and cGMP are responsible for the inhibition. In the present report, effects of these putative crowding factors on worm development in vivo were examined. At 7 days postinfection the proximal end of the host's intestine was catheterized and perfused with test solution. The test solution contained 28 nM cGMP, 250 microM glucosaminic acid, 120 mM succinate, and 40 mM acetate. The solution was perfused by a peristaltic pump at a rate of 50 ml/day. At 2 wk postinfection, worms were recovered for subsequent analysis. Worms developing in the presence of crowding factors were 53% less in wet weight than control worms. Carbohydrate concentrations in worms from experimental groups were not different from those in control groups; therefore, the inhibition in growth was probably not due to carbohydrate deprivation. Worms from experimental groups had fewer immature, mature, and gravid proglottids than did worms from control groups. The results are consistent with the hypothesis that the tested substances, which inhibit DNA synthesis in H. diminuta in vitro, are a part of the cause of the crowding effect in vivo.

Topics: Acetates; Animals; Carbohydrate Metabolism; Carbohydrates; Cyclic GMP; Female; Glucosamine; Hymenolepiasis; Hymenolepis; Rats; Succinates; Weight Gain

Worm-conditioned saline (WCS) was prepared by incubating Hymenolepis diminuta from crowded infections for 12 hr in a balanced salt solution. The effect of the WCS on the incorporation of [3H] thymidine into DNA in the anterior regions of fresh H. diminuta was compared to effects produced by the cyclic nucleotides in the WCS. Cyclic AMP and cGMP were found in the WCS, and cGMP but not cAMP (at the concentration in WCS) caused some inhibition of DNA synthesis. For further study of the effects of cyclic nucleotides, worms were incubated with theophylline, caffeine, 3-isobutyl-1-methyl xanthine, 2-deoxy cGMP, and L-ascorbic acid, all of which produced some inhibition of [3H] thymidine incorporation. Treatment of WCS with 3',5' cyclic nucleotide phosphodiesterase abolished part of its inhibitory activity, i.e., that part presumed to be due to cGMP. When worms were incubated in the presence of succinate, acetate, D-glucosaminic acid, and cGMP simultaneously and in the concentrations each was found in the WCS, DNA synthesis was inhibited to a degree equal to that found in the WCS. Thus these substances apparently represent the putative crowding factors in the WCS. WCS prepared with worms from different population densities contained the same levels of cAMP but varied in content of cGMP, which decreased as the worm density increased. WCS prepared with patent worms contained high levels of cAMP, but the same amounts of cGMP as WCS prepared with 10-day-old worms. At least some inhibitors of cyclic nucleotide phosphodiesterase inhibited the secretion of cGMP by the worms. Levels of cGMP in the host intestine varied with the presence or absence of worms, number of worms, and area of the intestine.

Topics: Animals; Ascorbic Acid; Cyclic GMP; DNA Replication; Hymenolepiasis; Hymenolepis; Intestines; Male; Nucleotides, Cyclic; Phosphodiesterase Inhibitors; Rats