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Journal of Pharmacology and Experimental Therapeutics

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OtherGASTROINTESTINAL PHARMACOLOGY

Stabilization of Vasoactive Intestinal Peptide by Lipids

Gennady Gololobov, Yasuko Noda, Simon Sherman, Israel Rubinstein, Janina Baranowska-Kortylewicz and Sudhir Paul
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 753-758;
Gennady Gololobov
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Yasuko Noda
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Simon Sherman
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Israel Rubinstein
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Janina Baranowska-Kortylewicz
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Sudhir Paul
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Abstract

An anionic phospholipid, phosphatidylglycerol (PG), induced vasoactive intestinal peptide (VIP) to adopt a helical conformation, determined by circular dichroism studies. PG inhibited the trypsin-catalyzed, antibody-catalyzed and uncatalyzed cleavage of VIP, measured by radiometric and HPLC methods. Phosphatidylcholine, a neutral lipid, did not alter the circular dichroism spectra of VIP, and it was without detectable effect on the rates of VIP cleavage. Trypsin-catalyzed cleavage of Boc-Ile-Glu-Arg-methylcoumarinamide, a substrate unrelated in sequence to VIP, proceeded at equivalent rates in the absence and presence of PG, which suggests that the phospholipid did not exert a nonspecific inhibitory effect on the enzyme. Study of the kinetics of antibody-catalyzed VIP cleavage indicated that the inhibition by PG was due to decreased affinity for VIP, suggested by observations of increased Km values and unalteredVmax values. Incorporation of VIP in the liposomes and the liposomal surface permitted maintenance of the peptide in essentially undegraded form at 37°C for 8 days. The longevity of liposomal VIP administered i.v. to mice was increased by about 5-fold compared with aqueous VIP. These observations indicate that certain phospholipids and liposomes can be applied to circumvent the rapid loss of VIP in vitro and in vivo due to degradative processes.

Footnotes

  • ↵1 Supported by U.S. Public Health Service grants HL44126, AI31268, DE10347 and DE00386.

  • Send correspondence and reprint requests to: Sudhir Paul, Ph.D., Department of Pathology, University of Texas Houston Medical School, 6531 Fannin, Houston, TX 77030.paul{at}casper.med.uth.tmc.edu

  • Abbreviations:
    BSA
    bovine serum albumin
    CD
    circular dichroism
    PG
    phosphatidylglycerol
    PC
    phosphatidylcholine
    TCA
    trichloroacetic acid
    VIP
    vasoactive intestinal peptide
    • Received July 2, 1997.
    • Accepted January 16, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 2
1 May 1998
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OtherGASTROINTESTINAL PHARMACOLOGY

Stabilization of Vasoactive Intestinal Peptide by Lipids

Gennady Gololobov, Yasuko Noda, Simon Sherman, Israel Rubinstein, Janina Baranowska-Kortylewicz and Sudhir Paul
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 753-758;

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OtherGASTROINTESTINAL PHARMACOLOGY

Stabilization of Vasoactive Intestinal Peptide by Lipids

Gennady Gololobov, Yasuko Noda, Simon Sherman, Israel Rubinstein, Janina Baranowska-Kortylewicz and Sudhir Paul
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 753-758;
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