GENERAL AND COMPARATIVE ENDOCRINOLOGY 58, 150-1.58 (1985) Regulatory Peptides (Glucagon, Somatostatin, Substance P, and VIP) in the Brain and Gastrointestinal Tract of Ambystoma mexicanum J.M. CONLON,~ M. BALLMANN,AND R. LAMBERTS Clinical Research Group for Gastrointestinal Endocrinology of the Max-Planck-Gesellschaft, and Department of Medicine, University of Giittingen, Gdttingen, West Germany Accepted June 19, 1984 The concentrations of immunoreactive components of glucagon, somatostatin, substance P, and vasoactive intestinal polypeptide (VIP) in the brain, stomach, and gut of the neotenic Mexican axolotl (Ambystoma mexicanurn) were determined by radioimmunoassay using antibodies of defined regional specificity. The molecular forms of the immunoreactive com- ponents were analyzed by high-performance liquid chromatography (HPLC). The concen- trations and molecular forms of somatostatin and VIP in axolotl brain were comparable to the concentrations in mammals but the substance P-like immunoreactivity was resolved by HPLC into components with the retention times of physalaemin and substance P together with their oxidized forms. No glucagon-like material was detected in the axolotl brain. The concentrations of substance P and VIP in the A. mexicanum digestive tract were appreciably lower than in the mammalian digestive tract and the VIP-like material did not coelute with porcine VIP. Somatostatin-14 represented the major molecular form in the axolotl stomach and gut. The distribution and molecular properties of the glucagon-like peptides in the axolotl digestive system were markedly different from these parameters in mammalian gut. Glucagon-like material is present only in low amounts in porcine and human stomach and, the concentration of enteroglucagon (N-GLI) in the gut is at least fiftyfold greater than pancreatic glucagon (C-GLI) concentrations. The axolotl stomach, in contrast, contains high levels of glucagon-like immunoreactive material and, in both stomach and gut, the levels of C-CL1 and N-GLI were comparable. The glucagon-like material was heterogeneous on HPLC and was resolved into two major components but no component with the retention time of mammalian glucagon was present. The immunochemical properties of the axolotl glucagon-like peptides indicate that they possess strong homology with mammalian glu- cagon in the lo- 18 and 25-29 regions of the molecule. o 1985 Academic PIWS, IIIC. Endocrinological investigations carried out originally in amphibia have frequently provided information that is relevant to subsequent investigations in the higher mammals. Physalaemin, first isolated from the skin of the South American leptodac- tylid frog Physalaemus fuscumaculatus (Erspamer et al., 1964), has been detected in a human lung small-cell carcinoma (Laz- arus et al., 1983) and a physalaemin-like peptide has been detected in rabbit stomach ’ To whom correspondence should be addressed at: Klinische Arbeitsgruppe der MPG, Gohlerstrasse lOd, D-3406 Giittingen W. Germany. (Lazarus et al., 1980). Similarly, kassinin, an amphibian tachykinin from the skin of the African frog, Kassina senegalensis (An- astasi et al., 1977), is homologous with neu- romedin K, isolated from porcine spinal cord (Kangawa et al., 1983). Bombesin, first isolated from the skin of Bomb&a bombina (Anastasi et al., 1971) has been shown to be biologically active in mammals (Bertaccini et al., 1974) and to be homolo- gous with mammalian gastrin-releasing peptide. Further studies have demonstrated considerable homology between sauvagine and corticotropin-releasing factor (CRF) and between caerulein and the CCK/gastrin 150 0016-6480/8.5 $1.50 Copyright 0 1985 by Academic Press, Inc. AU rights of reproduction in any form reserved.