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Differences in Action of PACAP-27 and PACAP-38 on Guinea Pig Gallbladder Smooth Muscle Using Synthetic C-terminally Modified PACAP Peptides

  • Mu-xin Wei
  • Satoru Naruse
  • Tsuyoshi Ozaki
  • Ping Hu
  • Victor Wray
  • Kiyoshi NokiharaEmail author
Article

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) occurs in two bioactive forms, PACAP-38 and PACAP-27 that have identical N-terminal sequences but differ by the presence of a C-terminal 11 residue elongation in the former. Although VIP and PACAP have several similar biological actions due to their amino acid sequence similarity, we have found that they evoke opposite responses in the guinea pig gallbladder smooth muscle, where PACAP induces contraction while VIP causes relaxation. In addition the response to PACAP-38 is four times lower than that of PACAP-27. In a previous study we have reported the role of the N-terminal α-helical regions of PACAP-27 which play a key role in gallbladder contraction. In the present study the biological action on the guinea pig gallbladder was investigated using a synthetic mini-library of C-terminally deleted peptides related to PACAP-38. The effects caused by residues within the C-terminus are not a result of a response via the M-receptor or Na+ channel, but most likely arise from a delicate balance between the differential effects of PACAP-38 on specific PAC1 and VPACs receptors.

Keywords

Guinea pig gallbladder PACAP VIP PAC1 receptor VPAC-receptor 

Abbreviations

ACh

Acetylcholine

CCK

Cholecystokinin

CD

Circular dichroism spectroscopy

NMR

Nuclear magnetic resonance spectroscopy

PACAP

Pituitary adenylate cyclase activating polypeptide

PAC-1

Type 1 receptor for PACAP

TTX

Tetrodotoxin

VIP

Vasoactive intestinal polypeptide

VPAC

Receptor for VIP and PACAP

Notes

Acknowledgments

A part of this work was supported by grants from the Ministry of Education, Culture, Science, and Technology, Japan Society for the Promotion of Science.

References

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Mu-xin Wei
    • 1
    • 2
  • Satoru Naruse
    • 2
  • Tsuyoshi Ozaki
    • 2
  • Ping Hu
    • 1
  • Victor Wray
    • 4
  • Kiyoshi Nokihara
    • 1
    • 3
    Email author
  1. 1.The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.National Institute of Physiological SciencesOkazakiJapan
  3. 3.Hipep LaboratoriesKyotoJapan
  4. 4.Department of Structural BiologyHelmholtz Centre for Infection ResearchBraunschweigGermany

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