Interactions of human secretin with sterically stabilized phospholipid micelles amplify peptide-induced vasodilation in vivo.
Secretin, a 27-amino acid neuropeptide, is a member of the glucagon/secretin/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides that elicits transient vasodilation in vivo. The purpose of this study was to determine whether association of human secretin with sterically stabilized phospholipid micelles (SSM) amplifies the vasorelaxant effects of the peptide in the peripheral microcirculation in vivo. We found that secretin in saline evoked significant concentration-dependent vasodilation in the intact hamster cheek pouch microcirculation (P < 0.05). This response was potentiated and prolonged significantly when secretin was associated with SSM (P < 0.05). Vasodilation evoked by secretin in saline and secretin in SSM was abrogated by VIP(10-28), a VIP receptor antagonist, but not by PACAP(6-38), a PACAP receptor antagonist, or Hoe140, a selective bradykinin B(2) receptor antagonist. Collectively, these data indicate that self-association of human secretin with SSM significantly amplifies peptide vasoreactivity in the intact peripheral microcirculation through activation of VIP receptors. We suggest that the vasoactive effects of human secretin in vivo are, in part, phospholipid-dependent.
Gandhi
Salil
S
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60612, USA.
Tsueshita
Takaya
T
Onyüksel
Hayat
H
Chandiwala
Rinku
R
Rubinstein
Israel
I
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D006801:Humans; D008823:Micelles; D010743:Phospholipids / Q000378:metabolism*; D012633:Secretin / Q000378:metabolism* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D008823:Micelles; D010743:Phospholipids; D014665:Vasodilator Agents; D012633:Secretin