The Action of Posterior Pituitary Extracts Upon Propulsion in the Small Intestine of Conscious Dogs

In 1909 Fodera and Pittau noted that injections of hypophysial extracts into dogs caused " la repetition de defecations ayant un caractere diarrheique et suivies de tenesme."In the same year Dale independently reported that extracts of the posterior lobes of ox pituitaries, boiled in acetic acid, filtered, and neutralized before use, caused an isolated strip of dog intestine to contract; and Bell, working with pithed rabbits, observed defaecation and increased peristalsis after injections of similar extracts supplied by Dale.Bell also announced that he had employed the extracts, without a single failure, in the treatment of several patients suffering from post-operative paralytic ileus, and recorded the reports of some of his colleagues who had been persuaded to use the extracts in similar cases.In the ensuing years numerous commercial preparations of pituitary extracts were put on the market, and much work was done in an attempt to throw the light of analytical experiment upon the empiricism of their use in clinical treatment.Although most authors were able to confirm that the extracts had a stimulating action upon various preparations of intestine, some, for example, Shamoff (1916), found them inhibitory.It was suggested by Roth (1917) that the differences in results could be attributed to the fact that insufficient attention had been paid to the presence of acid or preservative in many of the preparations.Detailed reviews of the early literature were made by Geiling (1926) and by Gruber and Robinson (1929).In 1925, however, Macdonald, using carefully made, neutralized, and preservative-free extracts, could find no specific stimulating action upon cat intestine, and suggested that what action there was could be attributed to a non-specific " histamine-like " substance present in extracts of tissues other than the pituitary gland.Gaddum (1928) confirmed that cat intestine was insensitive to pituitary preparations, but showed that isolated rabbit gut was powerfully contracted by a substance in pituitary extracts which could not be histamine.He also demonstrated that the active substance was present mainly in the " pressor " fraction of the extract, and that the co'on was contracted more forcibly that the jejunum.It thus appeared that, even after the elimination of unphysiological pH, preservative, and histamine, posterior pituitary extracts contained a substance which contracted the isolated intestine of all animals studied except the cat.(That cat intestine does, in fact, also respond to pitressin, though not to pitocin, was shown by Steggerda, Gianturco, and Essex, 1938.)The defaecation produced in normal animals, and the stimulation of isolated pieces of gut, led to the expectation that injections of pituitary extracts could be shown to cause