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 VIP is unordered in aqueous solution at room temperature but assumes appreciable a helix conformation in SSM. This conformational transition was amplified at 37 degrees 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 alpha helix in SSM. This process is associated with potentiation and prolongation of VIP-induced vasodilation in the in situ peripheral microcirculation.
Rubinstein
I
I
Department of Medicine, University of Illinois at Chicago, and West Side Department of Veterans Affairs Medical Center, 60612-7231, USA.
Patel
M
M
Ikezaki
H
H
Dagar
S
S
Onyüksel
H
H
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002147:Calmodulin / Q000008:administration & dosage / Q000494:pharmacology*; D002610:Cheek / Q000098:blood supply; D002942:Circular Dichroism; D006224:Cricetinae; D004357:Drug Synergism; D008297:Male; D008647:Mesocricetus; D008823:Micelles; D008833:Microcirculation / Q000187:drug effects; D010743:Phospholipids; D011487:Protein Conformation; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D002147:Calmodulin; D008823:Micelles; D010743:Phospholipids; D014660:Vasoactive Intestinal Peptide