Vasoactive Intestinal Peptide Stimulates Bone Resorption via a Cyclic Adenosine 3′,5′-Monophosphate-Dependent Mechanism*

Abstract

Vasoactive intestinal peptide (VIP) stimulated bone resorption in mouse calvaria in organ culture. The effect was dose dependent between 0.01–1.0 fig VIP/ml (3–300 nM). Stimulation over a period of 48 h was greater when the peptide was added in four staggered doses than if the same total dose was added at time zero. VIP-stimulated bone resorption was as great as that produced by two other polypeptides, epidermal growth factor and platelet-derived growth factor, which we have previously found to act via a prostaglandin (PG)-mediated mechanism. However, unlike these polypeptides, the action of VIP on bone was not blocked by inhibitors of PG synthesis, such as indomethacin or cortisol. RIA of bone culture medium showed no increase in the concentration of PGE₂ in the presence of maximum stimulatory concentrations of VIP. VIP rapidly enhanced (2. Pretreatment with PTH caused complete desensitization to a second challenge with PTH and partial heterologous desensitization to VIP, without altering PGE₂ responsiveness. We conclude that VIP acts to enhance bone resorption via a cAMP-dependent, PG-independent mechanism, which is probably similar to that induced by PTH.