Mulder H, Jongsma H, Zhang Y, Gebre-Medhin S, Sundler F, Danielsen N
Department of Cell and Molecular Biology, Lund University, Sweden.
Mol Neurobiol. 1999 Jun;19(3):229-53. doi: 10.1007/BF02821715.
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 beta-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.
初级感觉神经元具有双重作用，既是传入神经元，将感觉信息从外周传递到中枢神经系统，又是传出效应器，介导例如神经源性炎症。神经肽对于初级感觉神经元的这两种机制都至关重要。在传入功能中，它们除了作为主要递质外，还充当信使和调节剂；通过从外周终末释放，它们诱导传出反应，即“神经源性炎症”，其包括血管舒张、血浆外渗和免疫细胞募集。在本文中，我们介绍感觉神经肽家族的两个新成员：垂体腺苷酸环化酶激活多肽（PACAP）和胰岛淀粉样多肽（IAPP）。PACAP是一种类似于血管活性肠多肽的肽，主要存在于神经元成分中，而IAPP在结构上与降钙素基因相关肽有关，作为一种胰腺β细胞肽最为人所知；因此，它被认为是2型糖尿病中淀粉样沉积物的一个组成部分。在初级感觉神经元中，在正常情况下，这两种肽都主要在小尺寸神经细胞体中表达，提示其在伤害感受中起作用。在轴突切断后，PACAP的表达迅速被诱导，而IAPP的表达则降低。PACAP的这种调节表明它在神经损伤期间起保护作用，而IAPP的调节可能表明它在正常情况下是一种兴奋性信使。相反，在局部佐剂诱导的炎症中，这两种肽的表达都迅速被诱导。对于IAPP，对IAPP缺陷小鼠的研究支持IAPP是一种促伤害感受肽的观点，因为这些突变小鼠在用福尔马林刺激时表现出伤害感受反应降低。
