Different regulatory tissue profiles may explain the different clinical features of fore, mid and hind gut carcinoids

239 DIFFERENT REGULATORY TISSUE PROFILES MAY EXPLAIN THE DIFFERENT CLINICAL FEATURES OF FORE, MID AND HIND GUT CARCINOIDS E Harrison, K.D. Buchanan, C. Shaw, C.F. Johnston, Wellcome Research Laboratories, Department of Medicine, The Queen's University of Belfast, Belfast, BTI2 6BJ. Carcinoid tumours arising in fore, mid and hind gut have different clinical syndromes. This may be at least partly related to different regulatory peptides produced by the tumours. In order to assess this the regulatory peptide content of lung (n=17), stomach (n=3), ileal (n=15) and colon or rectum (n=l) were therefore studied by extraction of tissue followed by radioimmunoassay. All tumours contained large quantities of pancreastatin. All ileal tumours contained the tachykinins (substance P and neurokinin A) but tachykinins were not elevated in any other site. The lung tumours expressed in some instances pancreatic po]ypeptide, gastrin releasing peptide and calcitonin gene related peptide. Similar profiles were found in matched plasma samples of the patients. The regulatory peptide content of carcinoid tumours arising in different embryological sites is different and may explain the different clinical syndromes. Peripheral plasma hormonal profiles will aid detection of the primary origin of the tumour when this is clinically unapparent.

DIFFERENTIAL PROCESSING OF THE NEUROTENSIN/NEUROMEDIN N PRECURSOR IN BOVINE OCULAR TISSUES

R.G.J.Hayes I, c. Shaw I, C.F.Johnston I, P.Kitabgi 2 and K.D.Buehanan I. iDepartment of Medicine, The Queen's University of Belfast, Northern Ireland and 2Institut Moleculaire et Cellulaire, CNRS, Sophia Antipolis, France. Neurotensin (NT) and neuromedin N (NN) occur in tandem in the same precursor flanked both N-terminally and C-terminally by paired basic amino acid cleavage sites. The processing of the common precursor in bovine ocular tissues has been studied using a battery of region-specific radioimmunoassays to both peptides. In retinal extracts, the molar concentration of NN was significantly higher (p<0.001) than NT, whereas in extracts of choroid/sclera and iris ciliary bodies, the molar concentration of NT was significantly higher (p<0.001) than NN. This discrepancy was confirmed by radioimmunoassay of reverse phase HPLC fractions of extracts. Using an antiserum which recognises the common C-terminal tripeptide of both peptides, a high degree of molecular heterogeniety was detected in extracts of all tissues. These data demonstrate complex and differential processing of the common precursor within a single organ system which may be of functional relevance.