Distribution of the VPAC2 receptor in peripheral tissues of the mouse.
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.
Harmar
Anthony J
AJ
Division of Neuroscience, School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, United Kingdom EH8 9JZ. tony.harmar@ed.ac.uk
Sheward
W John
WJ
Morrison
Christine F
CF
Waser
Beatrice
B
Gugger
Mathias
M
Reubi
Jean Claude
JC
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
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