Expression and fine mapping of murine vasoactive intestinal peptide receptor 1

Vasoactive intestinal peptide (VIP) plays multiple roles in the nervous, endocrine, and immune systems as a neurotransmitter, a hormone, and a cytokine. VIP is widely distributed in neurons of the central and peripheral nervous systems (CNS/PNS), and recently has been found to be an important neuroprotective agent. VIP actions are mediated through specific G protein-coupled receptors. We have cloned the cDNA of VIP receptor subtype 1 (VIPR1(dagger) or VPAC(1) and have demonstrated the quantitative expression profile in mice. Fluorometric real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that VPAC(1) is expressed in all tissues examined. Expression was highest in the small intestine and colon followed by the liver and brain. The high level of VPAC(1) expression in forebrain and cerebellum suggests that VPAC(1) may mediate the neuroprotective effect of VIP. We have refined the chromosomal localization of the mouse, rat, and human VPAC(1) genes. This fine mapping of the VPAC(1) gene extends the respective regions of synteny between the distal region of mouse chromosome 9, rat chromosome 8q32, and human chromosome 3p2l.33-p21.31. Thus, VPAC(1) constitutes a functional-positional candidate for the tumor-suppressor function mapped to human 3p22-p21 where loss-of-heterozygosity is observed in small-cell lung carcinoma (SCLC) cell lines and primary tumors. Availability of the cDNA sequences for mouse VPAC(1) will facilitate the generation of VPAC(1) null mutant animals. Such studies will ultimately enhance our understanding of the role of VIP in the nervous system.