Treating diarrhoea: what might the pituitary offer?
Authors: OVE LUNDGREN
Journal: Gut (1997)

Treating diarrhoea: what might the pituitary oVer?Administration of cholera toxin to an animal can protect it against subsequent administration of the toxin or viable Vibrio cholerae.This protection is usually explained in terms of neutralisation of the toxin by secretory IgA before it penetrates the intestinal mucosa.In 1984 Lange and Lönnroth 1 reported that extracts from hypophysis, brain and jejunal mucosa, obtained from rats immunised with cholera toxin administered intravenously or orally, attenuated fluid secretion induced by cholera toxin in jejunal loops.This eVect was not seen with extracts from other organs (pancreas, spleen, adrenal glands) or from control rats.The antisecretory activity of the pituitary material, known as antisecretory factor (ASF), increased as the number of immunisations increased.ASF was found to be a protein with a molecular mass considerably lower than that of IgA.This observation and the origin of ASF suggested that it is not secretory IgA.Subsequently, Lange and Lönnroth 2 reported that ASF was also found in bile and milk from rats immunised with cholera toxin.Further studies demonstrated antisecretory activity in the pituitary in rats, pigs and humans who had not been immunised against cholera toxin. 3Conventional biochemical separation techniques were used initially to try to isolate and characterise ASF. 3 The ASF bioassay comprises inhibition of cholera toxin induced fluid secretion in rat jejunal loops.The apparent molecular mass of ASF varied widely from 16 to 60 kDa in diVerent reports, as did its isoelectric point, [2][3][4] suggesting that there are more than one ASF.Eventually an ASF was cloned from human pituitary glands (recombinant ASF, rASF). 5rASF was found to be a new protein comprised of 382 amino acids with a molecular mass of 41.14 kDa.This substance was reported to inhibit cholera toxin induced fluid secretion at a dose of 10 -11 mole given intravenously to 200-250 g rats.On immunohistochemical examination of the pituitary gland, rASF was detected in cytoplasmatic granules in a moderate number of adenohypophysic cells.ASF eVects both the transport of intestinal fluid and also the histological changes induced by certain enterotoxins.In a previous report 6 and in one published in this issue (see page 642), Lange, Lönnroth and collaborators have investigated the eVects of ASF on the histological changes induced by Clostridium diYcile toxin A in the rat intestine.This toxin causes severe damage to the intestinal mucosa within hours, including villous destruction and mucosal bleeding.The toxins produced by C diYcile are probably of great importance in the pathophysiology of pseudomembranous enterocolitis.In the previous report 6 two ASFs were isolated from the rat pituitary gland, one of which was eVective in preventing the development of damage to the intestinal mucosa.In this issue rASF was tested in the same animal model using C diYcile toxin A. Furthermore, Johansson et al studied the eVect of rASF on the secretion and tissue damage caused by okadaic acid, a substance involved in food poisoning caused by shellfish.rASF was eVective in preventing fluid secretion induced by both agents.The histological damage induced by toxin A is on August 20, 2023 by guest.