Mechanism of action of cysteamine on duodenal alkaline phosphatase.
A single s.c. injection of cysteamine-HCl, a potent duodenal ulcerogen, drastically decreased duodenal alkaline phosphatase (DAP) activity in mucosal cells. The effect was detectable 4 hr after the injection of cysteamine, it was the most prominent at 12 hr and lasted less than 24 hr after the ulcerogen administration. Under the same experimental conditions cysteamine did not affect alkaline phosphatase activity in the liver. Furthermore, ethanolamine, the toxic but nonulcerogenic derivate of cysteamine, had no effect on the DAP activity if given in equimolar quantities. Thus, the effect of DAP activity seems to be a property of the duodenal ulcerogen, related only to the target organ, i.e. duodenal mucosa. Since cimetidine administration and pylorus ligation, which both abolish HCl hypersecretion provoked by cysteamine, did not "protect" the enzyme from the depletion, it is hard to believe that gastric acid hypersecretion could be responsible for the enzyme depletion provoked by the ulcerogen. Dopamine metabolism disorders, induced by cysteamine administration in the brain and duodenal mucosa, are not causally related to DAP-depletion either. Cysteamine most probably inhibits the DAP activity by three different mechanisms, by one acting directly on the enzyme molecules and by two others acting indirectly, through its adrenocorticolytic and stresogenic effects.
D000315:Adrenalectomy; D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003543:Cysteamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000201:enzymology; D004386:Duodenum / Q000201:enzymology*; D019856:Ethanolamine; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000201:enzymology; D009570:Nitriles / Q000494:pharmacology; D011706:Pyloric Antrum; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004983:Ethanolamines; D009570:Nitriles; D001971:Bromocriptine; D019856:Ethanolamine; D003543:Cysteamine; D002927:Cimetidine; C005557:propionitrile; D000469:Alkaline Phosphatase; D004298:Dopamine