Immunohistochemical localization of the VIP1 receptor (VPAC(1)R) in rat cerebral blood vessels: Relation to PACAP and VIP containing nerves

The two structurally related peptides, vasoactive intestinal polypeptide (V IP) and pituitary adenylate cyclase activating polypeptide (PACAP), are pre sent in cerebral vascular nerve fibers. Biologic actions of VIP are exerted through two receptors, VPAC(1) and VPAC(2), having similar binding affinit y for both VIP and PACAP. In the current study, the authors have developed a specific antibody against the rVPAC(1) receptor to examine the localizati on of rVPAC(1) immunoreactivity in cerebral arteries and arterioles of the rat by immunohistochemistry using fluorescence confocal microscopy. Specifi city of the antiserum was ensured by immunoblotting and immunocytochemistry of cells transfected with cDNA encoding the different PACAP-VIP receptor s ubtypes. The rVPAC(1) receptor immunoreactivity was localized to the plasma lemma of circularly orientated smooth muscle cells on superficial cerebral arteries and arterioles taken from the basal surface of the brain. By doubl e immunostaining VIP immunoreactive nerve fibers and, to a lesser extent, t hose containing PACAP were shown to have intimate contact with the receptor protein. Vasoactive intestinal polypeptide and PACAP containing cerebrovas cular nerve fibers were found in separate nerve populations with different distribution pattern and density. In brain sections processes of cortical V IP-, but not PACAP-, containing neurons seemed to innervate the rVPAC(1) re ceptor of pial arterioles on the brain surface. The current findings provid e the neuroanatomical substrate for a role of VIP and maybe PACAP in the re gulation of cerebral blood flow.