title: Supernatants from macrophages stimulated with microcystin-LR induce electrogenic intestinal response in rabbit ileum.
abstract: Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. This microorganism often forms toxic blooms in freshwater lakes and reservoirs for drinking water supply, producing serious disorders in humans and animals. Some have suggested that certain biological activities of microcystin may depend upon the stimulation of immune cells. Therefore, the aims of this research were to examine electrogenic intestinal secretion, in vitro, caused by the supernatants from macrophages stimulated with microcystin-LR, as well as to investigate the presence of interleukin-1beta and tumour necrosis factor-alpha in these supernatants. We found that the supernatants of macrophages stimulated with microcystin-LR (0.1, 0.3 and 1.0 microg/ml) caused electrogenic intestinal effects (change in short circuit currents (delta SCC)=57.6, 50.8 and 73.3, respectively, versus control=19.6 microA.cm(-2)) in a time-dependent way (microcystin-LR (1.0 microg/ml)=63.2, 108.8, 120.4 and 132.3 microA.cm(-2) at time 0, 40, 50 and 60 min., respectively). In addition, the intestinal secretory activity present in these supernatants was blocked (57%) by the prior treatment of macrophages with dexamethasone. We also demonstrated that microcystin-LR (0.1, 0.3 and 1.0 ,microg/ml) is capable of stimulating the synthesis of tumour necrosis factor-alpha (375.4, 369.0 and 610.8 pg/ml, respectively, versus control=165.0 pg/ml) and interleukin-1beta (198.9, 189.3 and 522.1 pg/ml, respectively, versus control=39.7 pg/ml). These findings demonstrate that microcystin-LR induces the release of interleukin-1beta and tumour necrosis factor-alpha by peritoneal macrophages in vitro, and that the supernatants from these macrophages induce electrogenic secretion in rabbit ileal mucosa.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza-CE, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Rocha
authors.forename: J J
authors.initials: JJ
authors.lastname: Sidrim
authors.forename: A M
authors.initials: AM
authors.lastname: Soares
authors.forename: G C
authors.initials: GC
authors.lastname: Jimenez
authors.forename: R L
authors.initials: RL
authors.lastname: Guerrant
authors.forename: R A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: A A
authors.initials: AA
authors.lastname: Lima
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C057862:cyanoginosin LR