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Submitted on August 15, 2003
Accepted on November 6, 2003
1 Division of Neuroscience (A.J.H., W.J.S., C.F.M.), School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, 1 George Square, Edinburgh EH89JZ, U.K.; Institute of Pathology (B.W., M.G., J.C.R.), University of Berne, Murtenstrasse 31, CH - 3010 Berne, Switzerland.
* To whom correspondence should be addressed. E-mail: Tony.Harmar{at}ed.ac.uk.
The neuropeptide vasoactive intestinal peptide (VIP) exerts its actions through two structurally related G protein-coupled receptors (VPAC1 and VPAC2). Pituitary adenylate cyclase activating polypeptide (PACAP) is also a potent agonist of VPAC1 and VPAC2 receptors, as well as of a third, PACAP-specific receptor (PAC1). We report here the distribution of the VPAC2 receptor in peripheral tissues of the mouse, determined by receptor autoradiography using [125I]-VIP and the selective VPAC2 receptor agonist [125I]-Ro25-1553 in wild-type and VPAC2 receptor null mice. In addition, displacement experiments with the VPAC2-selective agonist Ro25-1553 and the VPAC1-selective agonist [K15,R16,L27]VIP-(1-7)/GRF- (8-27) were performed using the universal radioligand [125I]-VIP. The VPAC2 receptor is found predominantly in smooth muscle (in blood vessels and in the smooth muscle layers of the gastrointestinal and reproductive systems), in the basal part of the mucosal epithelium in the colon, in the lung, in the vasculature of the kidney, in the adrenal medulla and in the retina. Unexpectedly, the receptor was also present in thyroid follicular cells and in 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 VPAC2 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.
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