Conformation and vasoreactivity of VIP in phospholipids: effects of calmodulin

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 V...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 1999-12, Vol.20 (12), p.1497-1501
Main Authors: Rubinstein, Israel, Patel, Manisha, Ikezaki, Hiroyuki, Dagar, Sumeet, Önyüksel, Hayat
Format: Article
Language:English
Subjects:
Animals
Arteriole
Arterioles - drug effects
Calmodulin - administration & dosage
Calmodulin - pharmacology
Cheek - blood supply
Circular Dichroism
Cricetinae
Drug Synergism
Hamster
Intravital microscopy
Male
Mesocricetus
Micelles
Microcirculation
Microcirculation - drug effects
PEG-DSPE
Phospholipids
Protein Conformation
Sterically stabilized micelles
Vasoactive Intestinal Peptide - administration & dosage
Vasoactive Intestinal Peptide - chemistry
Vasoactive Intestinal Peptide - pharmacology
Vasodilation - drug effects
Vasopressin
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Summary: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.
ISSN:0196-9781
1873-5169
DOI:10.1016/S0196-9781(99)00161-8