Helodermin is a vasoactive intestinal peptidelike peptide in the salivary gland venom of the lizard Heloderma suspectum. Helodermin-like immunofluorescence was observed in the parafollicular (C) cells in several mammals and in the C cell homologues of the chicken ultimobranchial gland. Thus, helodermin-like peptides coexist with calcitonin. The results of radioimmunoassay agreed with the immunocytochemical rindings. HPLC of rat thyroid extracts revealed one major peak of helodermin-like immunoreactivity, which eluted in a position close to that of lizard helodermin. Helodermin stimulated basal thyroid hormone secretion and colloid droplet formation in conscious mice. The effect of large doses of helodermin was quite long-lasting and the maximal response occurred after 2-6 hr. In addition, helodermin suppressed the incorporation of calcium into bone in conscious rats. The findings suggest that helodermin-like peptides in C cells may be involved in the local regulation of thyroid hormone secretion and in the maintenance of calcium homeostasis.Helodermin is an amidated 35-amino acid peptide isolated from salivary gland venom of the Gila monster lizard (Heloderma suspectum) (1, 2). Helodermin displays sequence homologies with peptides of the secretin family (1-4). Not surprisingly, helodermin exerts secretin-like and vasoactive intestinal peptide (VIP)-like actions in several biological systems (5-7).Immunochemical analyses have revealed small amounts of helodermin-like material in extracts of brain, salivary glands, and intestines of mammals (8,9). Recently, we showed helodermin-like immunoreactivity in cells in thyroid medullary carcinomas and parafollicular (C)-cell adenomas, where the helodermin-like material was found to coexist with calcitonin (CT) (10). The occurrence of helodermin-like immunoreactivity in normal human C cells suggested that helodermin-like peptides are normal constituents of such cells (10).This study confirms the presence of helodermin-like peptides in thyroid C cells of several mammals. Immunoreactive helodermin was determined by RIA and analyzed by HPLC. The effect of synthetic helodermin on thyroid hormone secretion was tested in mice, while its effect on calcium incorporation in bone was studied in rats.
MATERIALS AND METHODSTissue Material. Specimens from thyroid glands (at least ten from each species) were collected for immunocytochemistry and RIA from chickens, mice (NMRI), rats (SpragueDawley), hamsters, guinea pigs, rabbits, pigs, cows, and humans, and ultimobranchial glands (UBG) were collected from chickens. In addition, specimens from salivary glands, heart, lungs, gastrointestinal tract (esophagus, stomach, duodenum, jejunum, and colon), liver, pancreas, spleen, and kidneys of rats (200-g body weight) and pigs were collected.Immunocytochemistry. Helodermin antiserum. Antisera were raised in rabbits against unconjugated synthetic helodermin (Peninsula Laboratories). The peptide, 0.5 mg in 1 ml of 0.9% NaCl, was emulsified with 1.0 ml of Freund's complete adjuvant (Difco)...