The VIP₂ receptor: Molecular characterisation of a cDNA encoding a novel receptor for vasoactive intestinal peptide

Abstract

We have cloned and sequenced a cDNA (RPR4) encoding a new member of the secretin/calcitonin/parathyroid hormone (PTH) receptor family. RPR4 was identified by PCR of rat pituitary cDNA, and a full-length clone was isolated from a rat olfactory bulb cDNA library. When RPR4 was functionally expressed in COS 7 cells, cyclic adenosine monophosphate (cAMP) production was stimulated by vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptides (PACAP-38 and PACAP-27) and helodermin, with equal potency. Peptide histidine isoleucine (PHI) and rat growth hormone releasing hormone (rGHRH) also stimulated cAMP production at lower potency. This suggests that RPR4 encodes a novel VIP receptor which we have designated the VIP 2 receptor. In situ hybridisation showed that mRNA for this receptor was present mainly in the thalamus, hippocampus and in the suprachiasmatic nucleus.Vasoactive intestinal peptide (VIP); G protein-linked receptor; Rat pituitary; Rat olfactory bulb; cDNA cloning

Pituitary adenylate cyclase-activating polypeptide is an autocrine inhibitor of mitosis in cultured cortical precursor cells

“…In freshly dissected cortex tissue, significant quantities of PACAP were detected (Table 1) peptide activation of intracellular signaling was examined. We measured cAMP levels after peptide treatment because currently defined receptors couple to this pathway (11,(13)(14)(15)(16). PACAP elicited a 5-fold increase in cAMP levels, with a plateau at 0.1 nM, indicating that precursors possess a PACAP response system (Fig.…”

“…Type I receptors are PACAP-preferring, binding PACAP at nanomolar concentrations while binding VIP in the micromolar range (14). In contrast, type II receptors exhibit nanomolar affinities for both peptides (15,16). In the present study, we have defined the effects of PACAP on embryonic rat cortical precursors in culture.…”

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

“…PACAP exerts a wide range of biological effects notably in the brain where the peptide acts as a neuromodulator, a neurohormone and a neuroprotective agent (Vaudry et al, 2000). The multiple actions of PACAP are mediated through interaction with three types of receptors that is the PACAP-specific receptor (PAC1-R), and the PACAP/VIP mutual receptors VPAC1-R and VPAC2-R (Ishihara et al, 1992;Lutz et al, 1993;Spengler et al, 1993).…”

Mutations in the Second Cytoplasmic Loop of the Rat Parathyroid Hormone (PTH)/PTH-related Protein Receptor Result in Selective Loss of PTH-stimulated Phospholipase C Activity

“…The lack of sequence homology between PTH/PTHrP receptors and all but a few of the other G protein-coupled receptors, however, justifies classifying them as members of a distinct family (1), which includes two mammalian receptors each for PTH or PTHrP (2, 3), vasoactive intestinal peptides (4,5), and corticotrophin-releasing hormone (6), and receptors for secretin (7), calcitonin (8), glucagon-like peptide 1 (9), growth hormonereleasing hormone (10), glucagon (11), pituitary adenylyl cyclase-activating peptide (12), gastric inhibitory peptide (13), and an orphan receptor in brain similar to the calcitonin receptor (14). Receptors from this family are not limited to vertebrates, as two insect diuretic hormone receptors (15) and a partial genomic clone from Caenorhabditis elegans (16) also are homologous.…”