title: Distribution of the VPAC2 receptor in peripheral tissues of the mouse.
abstract: The neuropeptide vasoactive intestinal peptide (VIP) exerts its actions through two structurally related G protein-coupled receptors (VPAC(1) and VPAC(2)). Pituitary adenylate cyclase-activating polypeptide (PACAP) is also a potent agonist of VPAC(1) and VPAC(2) receptors as well as of a third, PACAP-specific receptor (PAC(1)). We report here the distribution of the VPAC(2) receptor in peripheral tissues of the mouse, determined by receptor autoradiography using [(125)I]VIP and the selective VPAC(2) receptor agonist [(125)I]Ro25-1553 in wild-type and VPAC(2) receptor-null mice. In addition, displacement experiments with the VPAC(2)-selective agonist Ro25-1553 and the VPAC(1)-selective agonist [K(15),R(16),L(27)]VIP(1-7)/GRF(8-27) were performed using the universal radioligand [(125)I]VIP. The VPAC(2) receptor is found predominantly in smooth muscle (in blood vessels and in the smooth muscle layers of the gastrointestinal and reproductive systems), the basal part of the mucosal epithelium in the colon, lung, the vasculature of the kidney, adrenal medulla, and retina. Unexpectedly, the receptor was also present in thyroid follicular cells and acinar cells of the pancreas, tissues that have not been found to express the receptor in other species, and in very large amounts in the lung. Our data suggest novel functions of the VPAC(2) receptor and additional potential therapeutic uses of drugs acting at the receptor (including the treatment of erectile dysfunction), but our results also indicate that caution should be exercised in using the mouse as an animal model for the evaluation of VIP analogs intended for diagnostic or therapeutic use in man.
authors: Division of Neuroscience, School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, United Kingdom EH8 9JZ. tony.harmar@ed.ac.uk
authors: Anthony J
authors: AJ
authors: Harmar
authors: W John
authors: WJ
authors: Sheward
authors: Christine F
authors: CF
authors: Morrison
authors: Beatrice
authors: B
authors: Waser
authors: Mathias
authors: M
authors: Gugger
authors: Jean Claude
authors: JC
authors: Reubi
mesh_terms: D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001808:Blood Vessels / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism; D004703:Endocrine System / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D008208:Lymphatic System / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014566:Urogenital System / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; C089777:Ro 25-1553; C409214:vasoactive intestinal peptide (1-7)-GRF (8-27), Lys(15)-Arg(16)-Leu(27)-; D014660:Vasoactive Intestinal Peptide