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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Pituitary adenylate cyclase-activating polypeptide and islet amyloid polypeptide in primary sensory neurons : Functional implications from plasticity in expression on nerve injury and inflammation

Author

  • Hindrik Mulder
  • Helen Jongsma
  • Yanzhen Zhang
  • Samuel Gebre-Medhin
  • Frank Sundler
  • Nils Danielsen

Summary, in English

Primary sensory neurons serve a dual role as afferent neurons, conveying sensory information from the periphery to the central nervous system, and as efferent effectors mediating, e.g., neurogenic inflammation. Neuropeptides are crucial for both these mechanisms in primary sensory neurons. In afferent functions, they act as messengers and modulators in addition to a principal transmitter; by release from peripheral terminals, they induce an efferent response, 'neurogenic inflammation,' which comprises vasodilatation, plasma extravasation, and recruitment of immune cells. In this article, we introduce two novel members of the sensory neuropeptide family: pituitary adenylate cyclase-activating polypeptide (PACAP) and islet amyloid polypeptide (IAPP). Whereas PACAP, a vasoactive intestinal polypeptide-resembling peptide, predominantly occurs in neuronal elements, IAPP, which is structurally related to calcitonin gene-related peptide, is most widely known as a pancreatic β-cell peptide; as such, it has been recognized as a constituent of amyloid deposits in type 2 diabetes. In primary sensory neurons, under normal conditions, both peptides are predominantly expressed in small-sized nerve cell bodies, suggesting a role in nociception. On axotomy, the expression of PACAP is rapidly induced, whereas that of IAPP is reduced. Such a regulation of PACAP suggests that it serves a protective role during nerve injury, but that of IAPP may indicate that it is an excitatory messenger under normal conditions. In contrast, in localized adjuvant-induced inflammation, expression of both peptides is rapidly induced. For IAPP, studies in IAPP-deficient mice support the notion that IAPP is a pronociceptive peptide, because these mutant mice display a reduced nociceptive response when challenged with formalin.

Department/s

  • Diabetes - Molecular Metabolism
  • Neural Interfaces
  • Department of Experimental Medical Science
  • Neuroendocrine Cell Biology
  • Neuronano Research Center (NRC)

Publishing year

1999

Language

English

Pages

229-253

Publication/Series

Molecular Neurobiology

Volume

19

Issue

3

Document type

Journal article review

Publisher

Humana Press

Topic

  • Cell and Molecular Biology

Keywords

  • Amylin
  • Axotomy
  • Freund's complete adjuvant
  • IAPP
  • In situ hybridization
  • Knockout mice
  • Neurogenic inflammation
  • Neuropeptides
  • PACAP
  • β-cells

Status

Published

Research group

  • Diabetes - Molecular Metabolism
  • Neural Interfaces
  • Neuroendocrine Cell Biology
  • Neuronano Research Center (NRC)

ISBN/ISSN/Other

  • ISSN: 0893-7648