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

Primary sensory neurons serve a dual role as afferent neurons, conveying se nsory 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 affere nt functions, they act as messengers and modulators in addition to a princi pal transmitter; by release from peripheral terminals, they induce an effer ent response, "neurogenic inflammation," which comprises vasodilatation, pl asma extravasation, and recruitment of immune cells. In this article, we in troduce two novel members of the sensory neuropeptide family: pituitary ade nylate cyclase-activating polypeptide (PACAP) and islet amyloid polypeptide (IAPP). Whereas PACAP, a vasoactive intestinal polypeptide-resembling pept ide, predominantly occurs in neuronal elements, IAPP, which is structurally related to calcitonin gene-related peptide, is most widely known as a panc reatic beta-cen peptide; as such, it has been recognized as a constituent o f amyloid deposits in type 2 diabetes. In primary sensory neurons, under no rmal conditions, both peptides are predominantly expressed in small-sized n erve cell bodies, suggesting a role in nociception. On axotomy, the express ion of PACAP is rapidly induced, whereas that of IAPP is reduced. Such a re gulation of PACAP suggests that it serves a protective role during nerve in jury, but that of IAPP may indicate that it is an excitatory messenger unde r normal conditions.