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Pituitary adenylate cyclase-activating polypeptide and islet amyloid polypeptide in primary sensory neurons

Functional implications from plasticity in expression on nerve injury and inflammation

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Abstract

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.

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Authors and Affiliations

  1. Section for Molecular Signaling, Department of Cell and Molecular Biology, Lund University, PO Box 94, S-221 00, Lund, Sweden

    Hindrik Mulder

  2. Section for Neuroendocrine Cell Biology, Department of Physiology and Neuroscience, Lund University, Sweden

    Helen Jongsma, Yanzhen Zhang, Frank Sundler & Nils Danielsen

  3. Department of Medical Biochemistry, Lund University, Sweden

    Samuel Gebre-Medhin

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  1. Hindrik Mulder
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  2. Helen Jongsma
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Correspondence to Hindrik Mulder.

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Mulder, H., Jongsma, H., Zhang, Y. et al. Pituitary adenylate cyclase-activating polypeptide and islet amyloid polypeptide in primary sensory neurons. Mol Neurobiol 19, 229–253 (1999). https://doi.org/10.1007/BF02821715

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