Conformation and vasoreactivity of VIP in phospholipids: effects of calmodulin

The purpose of this study was to determine the conformation and vasorelaxan t effects of vasoactive intestinal peptide (VIP) self-associated with steri cally stabilized phospholipid micelles (SSM) and whether Calmodulin modulat es both of these processes. Circular dichroism spectroscopy revealed that V IP is unordered in aqueous solution at room temperature but assumes appreci able alpha helix conformation in SSM. This conformational transition was am plified at 37 degrees C and by a low concentration of calmodulin (0.1 nM). Suffusion of VIP in SSM elicited significant time- and concentration-depend ent potentiation of vasodilation relative to that elicited by aqueous VIP i n the in situ hamster cheek pouch (P < 0.05). This response was significant ly potentiated by calmodulin (0.1 nM). Collectively, these data indicate th at exogenous calmodulin interacts with VIP in SSM to elicit conformational transition of VIP molecule from a predominantly random coil in aqueous envi ronment to cr helix in SSM. This process is associated with potentiation an d prolongation of VIP-induced vasodilation in the in situ peripheral microc irculation. (C) 1999 Elsevier Science Inc.:Alt rights reserved.