Pituitary Adenylate Cyclase Activating Peptide (PACAP): An Experimental Study On the Expression and Regulation in the Peripheral Nervous System

Abstract: This thesis deals with PACAP and PACAP type-1 receptors in the sensory and autonomic parts of the peripheral nervous system. In the rat, PACAP is expressed in small-sized sensory neurons and in C-fibers. Unilateral transection of the sciatic nerve (axotomy) causes an upregulation of PACAP in medium-sized and large neurons, whereas the density of PACAP-IR fibers is decrea sed in the dorsal horn. In parasympathetic ganglia of the rat (the otic and sphenopalatine ganglia) PACAP expression is found in almost all nerve cell bodies together with VIP and NOS. The postganglionic fibers innervate e.g. cranial vessel and salivary glands. The rat adrenal medulla harbors a dense population of PACAP-IR fibers juxtaposed to PACAP type-1 receptor expressing chromaffin cells. This observation provides a neuroanatomical basis for the documented potency of PACAP in catecholamine biosynthesis and release from chromaffin cells. In the SCG of rat and mouse, PACAP is found in perineural "baskets" of preganglionic cholinergic fibers, but only rarely in neurons, whereas PACAP type-1 receptors are expressed in virtually all neurons. Upon axotomy or 6-OHDA treatment, PACAP expression is induced in a large number of neurons, whereas PACAP type-1 receptor expression is generally downregulated. The upregulation of PACAP after axotomy and 6-OHDA treatment is reminiscent of that of galanin. Culturing of rat and mouse SCG (0-48 h) leads to an upregulation in PACAP expression, albeit less extensive than after axotomy. During culture, PACAP type-1 receptors are downregulated, with the exception for a small number of neurons displaying an enhanced mRNA expression. PACAP addition to cultured SCG had no significant effect on cell survival or density of neurite outgrowth. The occurence of PACAP in nerve fibers and nerve cell bodies in sensory and autonomic ganglia provides a clue to the impor tance of this neuropeptide in the peripheral nervous system. Furthermore, data are accumulating suggesting a role for PACAP during the restoration process after neuronal injury both in sensory and autonomic neurons.