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Helodermin is a 35-amino acid peptide from the salivary gland venom of the lizard Heloderma Suspectum (Gila Monster), showing a high degree of sequence similarity with vasoactive intestinal pepetide (VIP), peptide histidine isoleucine (PHI) and secretin in its N-terminal moiety. Helodermin inhibits calcium incorporation into rat bones in vivo. Besides, the study showed that the helodermin augments PTH-induced bone resorption and strongly inhibits bone matriz apposition in the organ cultures of fetal rat calvaria.

Mechanism of action

The effects of helodermin on the osteoblast-like cells seem to be at least partially mediated by cAMP, with the finding that the cAMP increased in the osteoblast-like cells with helodermin while in other tissues the cAMP system was observed to be the major signaling pathway for helodermin. The effects of helodermin on the fetal rat calvaria cells seem to be exclusively mediated by a secretin-type receptor.

Application of Helodermins

A study showed that VIP-like peptide helodermin has direct effects on fetal rat bone cells in vitro. The effects of helodermin were similar to those observed with PTH, although equimolar concentrations of helodermin appeared to be at least 10-fold less potent. Helodermin enhanced the effects of PTH, in addition to the single effects on bone metabolism. Therefore, one of the major functions of helodermin-like peptides might be an enhancement of PTH-mediated effects on bone metabolism. There is the observation concerning helodermin has been the colocalization of helomin-like material with calcitonin in C cells of various species, suggesting that helodermin-like peptides might play a role as systemic hormonal mediators. The helodermins may have a direct effect on bone cell metabolism. The bioactivity of helodermin was evaluated by examining its effect upon canine vasoactivity. The potency of this activity of helodermin was significantly lower than that of VIP. Besides, the PHM (human PHI) was extremely lower than those of VIP and helodermin. Furthermore, the effect of intraarterial infusion of synthetic helodermin on femoral arterial blood flow in dogs flow in dogs lasted sighnificantly longer than that of VIP. Intravenous injection of synthetic helodermin exhibited VIP-liked cardiovascular effects in anesthetized dogs.

1. Bokvist, B. K., Gromada, J. L., Cummins, R. C., Glaesner, W., Mayer, J. P., Zhang, L., & Alsina-Fernandez, J. (2008). U.S. Patent Application No. 11/569,362.
2. Pfeilschifter, J., Naumann, A., Oechsner, M., & Ziegler, R. (1990). Effects of helodermin on fetal rat bone metabolism in vitro. Biochemical and biophysical research communications, 170(2), 576-581.
3. Robberecht, P., De Graef, J., Woussen, M. C., Vandermeers-Piret, M. C., Vandermeers, A., De Neef, P., ... & Christophe, J. (1985). Immunoreactive helodermin-like peptides in rat: a new class of mammalian neuropeptides related to secretin and VIP. Biochemical and biophysical research communications, 130(1), 333-342.
4. Naruse, S., Yasui, A., Kishida, S., Kadowaki, M., Hoshino, M., Ozaki, T., ... & Yanaihara, N. (1986). Helodermin has a VIP-like effect upon canine blood flow. Peptides, 7, 237-240.

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