Contractile action of heat-labile toxin of Bordetella parapertussis on aortic smooth muscles of pigs.
Using both vascular smooth muscle strips (VSMS) and cultured cells (VSMC) from aortas of pigs, the contractile action of Bordetella heat-labile toxin (HLT) purified from B. parapertussis was studied in an attempt to elucidate the mechanisms of its action. HLT induced contractions in VSMC in parallel with the increase of Ca2+-influx. The HLT-induced Ca2+-influx and contraction were not influenced by verapamil or diltiazem, though a certain extension of the lag period was seen. The contractile action of HLT on VSMS and VSMC was not influenced either by diltiazem or quinacrine; that on VSMC was not influenced by prednisolone, indomethacin, aspirin, CV-3988, FPL-55712, ruthenium red, or TEAC. On VSMS, prednisolone caused the extension of lag period following HLT exposure. The action of HLT on VSMS was inhibited by TMB-8, whereas that on VSMC was not though the extension of lag period was seen. The HLT-induced contraction in both VSMS and VSMC was completely inhibited by H-7. The contraction in VSMS, but not in VSMC, was inhibited by H-8. HLT did not induce specific activation of the protein kinases in VSMC. The addition of cGMP or cAMP brought about relaxation in the HLT-exposed VSMS contracting in maximum. HLT caused a significant increase in permeability of VSMC membrane to trypan blue, accompanied with contraction. Both HLT-induced contraction and increase in permeability were inhibited by dextran of M.W. 8,000, but not of M.W. 5,000. These results suggested that HLT acted on vascular smooth muscle cells by damaging the membrane permeability, but not by disturbing the known cascades or systems for physiological contractions, resulting in the increase in Ca2+-influx and then contractions.
Endoh
M
M
Department of Microbiology, School of Pharmaceutical Sciences, Kitasato University, Tokyo.
Nagai
M
M
Nakase
Y
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001427:Bacterial Toxins / Q000633:toxicity*; D001693:Biological Transport, Active / Q000187:drug effects; D001884:Bordetella; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D013552:Swine; D011503:Transglutaminases; D010566:Virulence Factors, Bordetella
D001427:Bacterial Toxins; D002121:Calcium Channel Blockers; D010566:Virulence Factors, Bordetella; C060969:dermonecrotic toxin, Bordetella; D011503:Transglutaminases; D002118:Calcium