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Conformation and vasoreactivity of VIP in phospholipids: effects of calmodulin  |
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| Authors: | Israel Rubinstein Manisha Patel Hiroyuki Ikezaki Sumeet Dagar Hayat nyüksel |
| Institution: | a Department of Medicine, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612–7231, USA;b Department of Bioengineering, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612–7231, USA;c Department of Pharmaceutics and Pharmacodynamics (M/C 865), College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612–7231, USA;d West Side Department of Veterans Affairs Medical Center, Chicago, IL 60612, USA |
| Abstract: | The purpose of this study was to determine the conformation and vasorelaxant effects of vasoactive intestinal peptide (VIP) self-associated with sterically stabilized phospholipid micelles (SSM) and whether calmodulin modulates both of these processes. Circular dichroism spectroscopy revealed that VIP is unordered in aqueous solution at room temperature but assumes appreciable α helix conformation in SSM. This conformational transition was amplified at 37°C and by a low concentration of calmodulin (0.1 nM). Suffusion of VIP in SSM elicited significant time- and concentration-dependent potentiation of vasodilation relative to that elicited by aqueous VIP in the in situ hamster cheek pouch (P < 0.05). This response was significantly potentiated by calmodulin (0.1 nM). Collectively, these data indicate that exogenous calmodulin interacts with VIP in SSM to elicit conformational transition of VIP molecule from a predominantly random coil in aqueous environment to α helix in SSM. This process is associated with potentiation and prolongation of VIP-induced vasodilation in the in situ peripheral microcirculation. |
| Keywords: | Microcirculation Arteriole Intravital microscopy Sterically stabilized micelles Circular dichroism PEG-DSPE Vasopressin Hamster |
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