Immunohistochemical Localization of the VIP₁ Receptor (VPAC₁R) in Rat Cerebral Blood Vessels: Relation to PACAP and VIP Containing Nerves

Abstract

The two structurally related peptides, vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP), are present in cerebral vascular nerve fibers. Biologic actions of VIP are exerted through two receptors, VPAC1 and VPAC2, having similar binding affinity for both VIP and PACAP. In the current study, the authors have developed a specific antibody against the rVPAC1 receptor to examine the localization of rVPAC1 immunoreactivity in cerebral arteries and arterioles of the rat by immunohistochemistry using fluorescence confocal microscopy. Specificity of the antiserum was ensured by immunoblotting and immunocytochemistry of cells transfected with cDNA encoding the different PACAP-VIP receptor subtypes. The rVPAC1 receptor immunoreactivity was localized to the plasmalemma of circularly orientated smooth muscle cells on superficial cerebral arteries and arterioles taken from the basal surface of the brain. By double immunostaining VIP immunoreactive nerve fibers and, to a lesser extent, those containing PACAP were shown to have intimate contact with the receptor protein. Vasoactive intestinal polypeptide and PACAP containing cerebrovascular nerve fibers were found in separate nerve populations with different distribution pattern and density. In brain sections processes of cortical VIP-, but not PACAP-, containing neurons seemed to innervate the rVPAC1 receptor of pial arterioles on the brain surface. The current findings provide the neuroanatomical substrate for a role of VIP and maybe PACAP in the regulation of cerebral blood flow.

Location and Function of VPAC1, VPAC2 and NPR-C Receptors in VIP-Induced Vasodilation of Porcine Basilar Arteries

“…The VPAC 1 agonist induces NO-and endothelial-dependent vasodilation over the same concentration range as VIP, which is in agreement with the immunocytochemical findings that this receptor is located on the endothelium. This is in contrast to a previous study, which identified VPAC 1 receptors on vascular smooth muscle cells of rat superficial cerebral arteries (Fahrenkrug et al, 2000). This highlights a possible species difference or a difference between the distributions of the VPAC 1 receptor in basilar and superficial cerebral arteries (i.e.…”

Cortical GABA Interneurons in Neurovascular Coupling: Relays for Subcortical Vasoactive Pathways

“…Particularly, mRNAs for VPAC1 receptors that are reputed to mediate dilatation in pial arteries (Yaksh et al, 1987;Fahrenkrug et al, 2000), were expressed in smooth muscle cells of intracortical microvessels, and VIP elicited a potent dilatation in these microvessels. In contrast, the failure of CCK to alter microvascular tone correlated well with the lack of CCK receptor expression in microvascular smooth muscle, suggesting that this peptide is unlikely to directly couple flow to neuronal activity.…”

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Induces Relaxations of Peripheral and Cerebral Arteries, which are Differentially Impaired by Aging

“…In previous studies (Amenta et al 1991 ;Fahrenkrug et al 2000 ;Erdling et al 2013 ), the vascular effects of PACAP1-38 were investigated in segments of rat middle cerebral artery (MCA) by pressurized arteriography and in a wire myograph. The authors have found the same magnitude of concentration-dependent relaxations of the MCA, in arteries of rat dura, whereas in human meningeal arteries, PACAP1-38 induced weak relaxations (Arsalan et al 2013;Baun et al 2011 ).…”

“…The vascular actions of PACAP1-38 are more effective compared to those of PACAP1-27 (Huang et al 1992 ;Okazaki et al 1992 ). The vasodilator activity of PACAP has been documented in vessels of various organs (Nandha et al 1991 ;Ross-Ascuitto et al 1993 ) via three specific receptors (PAC1R and VPAC1R/VPAC2R), both of which are highly expressed in the cerebral and peripheral blood vessels (Fahrenkrug et al 2000 ;Nandha et al 1991 ). They are localized in the smooth muscle cells of cerebral arteries and arterioles (Fahrenkrug et al 2000 ;Amenta et al 1991 ).…”

“…The vasodilator activity of PACAP has been documented in vessels of various organs (Nandha et al 1991 ;Ross-Ascuitto et al 1993 ) via three specific receptors (PAC1R and VPAC1R/VPAC2R), both of which are highly expressed in the cerebral and peripheral blood vessels (Fahrenkrug et al 2000 ;Nandha et al 1991 ). They are localized in the smooth muscle cells of cerebral arteries and arterioles (Fahrenkrug et al 2000 ;Amenta et al 1991 ). In vivo studies on beagle dogs described that intravenous infusion of very low doses (0.01-10 pmol/min) of PACAP induced a concentration-dependent increase in blood flow in human skin and a concomitant decrease in systemic blood pressure (Cardell et al 1991 ;Nandha et al 1991 ;Naruse et al 1993 ).…”