title: Blocking by 2,4,6-triaminopyrimidine of increased tight junction permeability induced by acetylcholine in the pancreas.
abstract: 1. The permeability of the paracellular pathway in the isolated rabbit pancreas has been studied with the aid of 2,4,6-triaminopyrimidine. 2. Addition of 2,4,6-triaminopyrimidine (1--10 mM) to the bathing medium has no effect on the rate of fluid secretion or on protein, Na+, K+, Ca2+ and sucrose concentrations in the secreted fluid. 3. When 1 x 10(-5) M carbachol is also added to the 2,4,6-triaminopyrimidine-containing bathing medium, there is a marked reduction in the increase of the paracellular permeability for sucrose and Ca2+ found upon addition of carbachol alone. The enzyme secretion, induced by carbachol, is not affected. 4. The minimal concentration of 2,4,6-triaminopyrimidine in the bathing medium required to reach its maximal effect on the paracellular permeability is approx. 0.55 mM at pH 7.4. 5. The effect of 2,4,6-triaminopyrimidine on the paracellular permeability after carbachol stimulation is also present when 2,4,6-triaminopyrimidine is added 5 min after the addition of 1 x 10(-5) M carbachol. 6. 2,4,6-Triaminopyrimidine has no effect on the increases in enzyme secretion and sucrose permeability caused by 1 x 10(-8) pancreozymin C octapeptide. 7. 2,4,6-Triaminopyrimidine appears in the secreted fluid at a concentration of 50% of that in the bathing medium. Upon addition of 1 x 10(5) M carbachol this concentration increases up to 80%. 8. These results indicate that: (a) the increased paracellular permeability upon stimulation with carbachol is not caused by the enzyme secretion as such and (b) addition of 2,4,6-triaminopyrimidine prevents the carbachol-induced increase in permeability of a channel in the tight junction complex.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors
chemical_list: D007473:Ion Channels; D011743:Pyrimidines; C012070:2,4,6-triaminopyrimidine; D002217:Carbachol; D000109:Acetylcholine; D002118:Calcium