A. G. E. Pearse

ENKEPHALIN-LIKE IMMUNOREACTIVITY IN THE HUMAN GASTROINTESTINAL TRACT

Morphine has powerful actions on brain and gut. Peptides with opiate-like actions (endorphins, enkephalins) are known to be normal constituents of the brain and now enkephalin-like immunoreactivity has been shown in the gut. Enkephalin-like immunoreactivity was present in all areas of the gut with particularly high concentration in the antrum and significant amounts in the upper small intestine. Immunocytochemistry on 1 micronm serial sections revealed enkephalin-like immunoreactivity in numerous cells of the antral mucosa, in a few cells of the duodenal mucosa and pancreas, and in the myenteric plexus of the gallbladder, cystic ducts, bileduct, and other areas of the lower intestine. Gastrointestinal physiology appears to be partly regulated by locally acting hormones and enkephalin may be one of these. The established effects of morphine on the alimentary tract provide a clue to the possible physiological role of enkephalin.

NEURON-SPECIFIC ENOLASE IS PRODUCED BY NEUROENDOCRINE TUMOURS

Neuron-specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase, which was first found in extracts of brain tissue, and was later shown to be present in APUD (amine precursor uptake and decarboxylation) cells and neurons of the diffuse neuroendocrine system but not in other peripheral cells. 90 neuroendocrine neoplasias (APUDomas) (including islet-cell tumours, phaeochromocytomas, medullary thyroid carcinomas, oat-cell tumours, and APUDomas of the gut, pancreas, and lung) reacted strongly with antisera to NSE. In addition, large amounts of the enzyme were found by radioimmunoassay in the tumours (mean 1626 +/- 479 SEM ng of NSE/mg protein), whereas control non-endocrine neoplasias contained less than 15 ng NSE/mg protein. Thus NSE, a specific enzyme produced in the neural and endocrine systems, was found to be produced in considerable quantities by all types of APUDomas but not in any non-endocrine tumours. NSE seems to be a useful and easily detected marker which may be used to distinguish endocrine from nonendocrine neoplasias. Clinical detection of endocrine tumours is difficult and such tumours are often missed. Use of NSE as a marker may avoid this.

VASOACTIVE INTESTINAL PEPTIDE AND WATERY-DIARRHŒA SYNDROME

Abstract Six patients with the watery-diarrhœa syndrome (pancreatic cholera) were found to have raised plasma levels and/or high tumour content of vasoactive intestinal peptide (V.I.P.), as measured by a specific radioimmunoassay. Positive immunofluorescence with V.I.P. antisera was obtained in two cases in which properly fixed tumour material was available. The known actions of V.I.P. accord well with the abnormalities found in the watery-diarrhœa syndrome. The availability of a plasma-V.I.P. assay may enable the diagnosis to be made before tumour metastasis occurs.

Immunocytochemical localization of substance P in mammalian intestine

SummaryIn mammalian intestine immunoreactive Substance P is localized not only in the plexuses of Auerbach and Meissner, as could be anticipated, but also in a number of basally situated, often basigranular, endocrine cells which have been identified tentatively as enterochromaffin.The presence of a neurohormone in cells of this type confirms their close association with the nervous system, noted by Masson (1924), and suggests that their postulated origin from the nervous system (Danisch, 1924) may well be correct.

Bifunctional reagents as vapour- and liquid-phase fixatives for immunohistochemistry

SynopsisOut of a total of eleven bifunctional reagents tested as fixatives for light microscopic immunohistochemistry, four were found satisfactory when applied in the vapour phase to freeze-dried blocks. These were diethylpyrocarbonate, as observed in carlier studies, dimethyladipimidate,p-benzoquinone, and diacetyl. Adequate but less satisfactory liquid-phase fixation was provided by three reagents (dimethyladipimidate, dimethylsuberimidate,p-benzoquinone).None of the eleven reagents gave optimal preservation of antigenicity and structure when tested at the ultrastructural level. Encouraging results were obtained withp-benzoquinone, however.

Pancreatic polypeptide in insulinomas, gastrinomas, vipomas, and glucagonomas.

In 33 patients studied with endocrine neoplasms of the pancreas more than half the tumours contained pancreatic polypeptide (P.P.) producing cells, and a high radioimmunoassayable concentration of P.P. was found in the tumour extracts. Plasma was available from 28 patients, and very high circulating P.P. concentrations were found in 18. The presence of P.P. in hepatic and lymphnode metastases indicates that its production by the primary neoplasm cannot be ascribed to incidental adherence of normal P.P. cells. Measurements of plasma P.P. levels should be a new aid to diagnosis of pancreatic tumours.

Immunohistochemical localisation of urogastrone to human duodenal and submandibular glands.

Urogastrone has been localised by immunostaining to granules of the cells of human duodenal (Brunners) glands and their ducts and of acinar cells in the human submandibular gland. The immunoreactive peptide is present in large quantities in duodenal glands and their secretory ducts. Urogastrone or human epidermal growth factor promotes cellular proliferation in vivo as well as in vitro and inhibits gastric acid secretion and may, therefore, be one of the duodenal factors inhibiting gastric activity. Thus it may have an important regulatory and protective function for the intestinal mucosa and may possibly become a useful therapeutic agent.

Cytochemical evidence for the neural crest origin of mammalian ultimobranchial C cells

SummaryThe cells of the neural crest have APUD properties at an early stage of devel opment (72 hours in the chick embryo). The FIF procedure provides a cytochemical means for their distinction.Using mouse embryos from mothers injected, intraperitoneally, 1 hr before removal, with l-DOPA (100 mg/kg), the peripheral stream of neural crest cells was clearly identifiable at the 7-somite stage (7–8 days). At the 10-somite stage (8–9 days) the cells were observed to invade the lateral processes of the foregut, and the foregut itself. A particularly high concentration of fluorescent APUD cells was observed in the anterior portion of the IVth pharyngeal pouch, destined to become the ultimobranchial body.At the 14-somite stage (11–12 days) the developing ultimobranchial body still contains fluorescent cells of neural crest origin.The implications of these findings on the question of the origin of the entire APUD series of endocrine polypeptide cells is discussed.

NEUROENDOCRINE EMBRYOLOGY AND THE APUD CONCEPT

In the Vertebrata the great majority of cells producing hormonal peptides belong to the APUD series and share its distinctive cytochemical and ultrastructural characteristics. According to the concept all members of the series are to be regarded as derivatives of neuroectoderm or of specialized (placodal) ectoderm.

Peptide hormone-like immunoreactivity in the gastrointestinal tract and endocrine pancreas of eleven teleost species

SummaryThe distribution of peptide hormone-like immunostaining in the gastrointestinal tract of 11 teleost species was investigated by immunofluorescence.Cells immunoreactive for somatostatin were found in the glandular epithelium of the stomach of four species and in the epithelium of the pyloric appendage of one species. The mid-gut epithelium contained cells reactive with antibodies to glucagon (three species), gastrin (five species), pancreatic polypeptide (five species), and substance P (two species). Cells immunoreactive for met-enkephalin were found in the epithelium of both the mid-gut and the stomach of six species.In six species in which the endocrine pancreas was investigated, insulin-, glucagon-, and somatostatin-like immunoreactivity was observed. Pancreatic polypeptide was definitely localised by immunostaining in cells of the endocrine pancreas of only one out of three species examined.Vasoactive intestinal polypeptide-, neurotensin-, bombesin-, and enkephalin-like immunoreactivity was identified in the gastrointestinal nerve fibres in various species.In view of the considerable species variation found, caution should be exercised in generalising about the peptides present in the gastrointestinal tract of fish.