PACAP-related peptide (PRP)-Molecular evolution and potential functions

PACAP-related peptide (PRP) and PACAP are structurally related peptides that are encoded in the same transcripts. In the past, it was believed that the mammalian PRPs are evolved from GHRHs in non-mammals. With the recent discovery of authentic GHRH and receptor genes in frog and fish, this review aims to (1) coin the name of all GHRH-like peptides in previous literature as PRPs and (2) provide the background for new research direction for PRP in vertebrates. As a goldfish receptor highly specific for PRP with distinct tissue distribution has previously been characterized, it is highly possible that PRP plays a physiological role in non-mammalian vertebrates and the function of PRP has somehow been lost in mammals as a consequence of the loss of its receptor in the genome. This information may provide clues to elucidate functions of PRP in the future. © 2007 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Analysis of a putative VPAC2 receptor from sturgeon shed light on molecular and functional evolution of VPAC2R in vertebrates

Session 7: Receptor and Pharmacology. No. O19Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are structurally related neuropeptides that exert multiple physiological effects in our body. Their actions are mediated through the activation of three receptors: PAC1R, VPAC1R, and VPAC2R. Despite the importance of these intercellular communicators, there is little information available for PACAP, VIP, and their receptors in extant early vertebrate species. In this study, a full-length VPAC2R cDNA was identified from a sturgeon species, Acipenser schrenskii. This cDNA is 1,498 bp in length encoding for a protein with 427 amino acids. Phylogenetic analysis showed that the sturgeon VPAC2R is structurally more similar to tetrapod VPAC2Rs than teleost VPAC2Rs or PHIRs. By real-time PCR, it was found that the sturgeon VPAC2R was widely distributed in various tissues, with the highest expression in gut and with moderate expression in liver and gonad. In functional cAMP assays, the sturgeon VPAC2R could be stimulated by mammalian and fish VIPs but not human and fish PHIs and PACAPs. These data suggested that the ability of VPAC2R to interact with PACAP evolved after the teleost/ tetrapod split in the tetrapod lineage. Moreover, the previously isolated fish PHIRs which are structurally related to VPAC2Rs in vertebrates may exist only in teleosts via the teleost-specific 3R genome duplication.The 9th International Symposium on VIP, PACAP and Related Peptides, Kagoshima, Japan, 5-8 October 2009. In Journal of Molecular Neuroscience, 2009, v. 42 n. 3, p. 28

Molecular Evolution of GPCRs: Secretin/secretin receptors

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Discovery of a new reproductive hormone in teleosts: Pituitary adenylate cyclase-activating polypeptide-related peptide (PRP)

Pituitary adenylate cyclase-activating polypeptide (PACAP)-related peptide (PRP) is a peptide encoded with PACAP in the same precursor protein. Non-mammalian PRPs were previously termed growth hormone-releasing hormone (GHRH)-like peptide, and was regarded as the mammalian GHRH homologue in non-mammalian vertebrates until the discovery of authentic GHRH genes in teleosts and amphibians. Although a highly specific receptor for PRP, which is lost in mammals, is present in non-mammals, a clear function of PRP in vertebrates remains unknown. Using goldfish as a model, here we show the expression of PRP and its cognate receptor in the brain-pituitary-gonadal (BPG) axis, thus suggesting a function of goldfish (gf) PRP in regulating reproduction. We found that gfPRP controls the expression of reproductive hormones in the brain, pituitary and ovary. Goldfish PRP exerts stimulatory effects on the expression of salmon gonadotropin-releasing hormone (sGnRH) in the brain, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in pituitary primary culture cells, but inhibits the expression of LH in the ovary. Using the same technique, we showed that gfPRP did not alter the mRNA level of growth hormone in the pituitary primary culture. In summary, we have discovered the first function of vertebrate PRP in regulating reproduction, which provides a new research direction in studying the neuroendocrine control of reproduction not only in teleosts, but also in other non-mammalian vertebrates. © 2011 Elsevier Inc.link_to_subscribed_fulltex

Molecular cloning and mRNA Distribution of pituitary adenylate cyclase-activating polypeptide (PACAP)/PACAP-related peptide in the lungfish

In this article, we report the isolation of a full-length cDNA clone encoding pituitary adenylate cyclase-activating polypeptide (PACAP)/PACAP- related peptide (PRP) from lungfish Protopterus dolloi. When comparing the deduced amino acid sequences, the lungfish PACAP was found to be highly conserved with other vertebrates; however, the PRP shares only lower levels of sequence identity with known PRP sequences. Consistently in phylogenetic analysis, the lungfish PRP, similar to sturgeon PRP, fails to cluster with other PRPs. In addition to the full-length clone, another cDNA encoding a short precursor that lacks the first 32 amino acids of the PRP was also isolated. Interestingly, similar isoforms were also identified in several nonmammalian vertebrates, and it was suggested that exon skipping of PRP/PACAP transcripts was a mechanism that regulated the expression ratio of PACAP to PRP in nonmammalian vertebrates. By real-time PCR, both long and short PRP/PACAP transcripts were found almost exclusively in the brain, and the short isoform is the more abundant transcript (3.7 times more), indicating that PACAP is the major product produced in lungfish brain. The expression patterns of lungfish and previously studied frog PRP/PACAP suggest that the PRP/PACAP gene in the tetrapod lineage may first express in the central nervous system; in the process of evolution, the functions of these peptides diversified and were later found in other tissues. © 2009 New York Academy of Sciences.link_to_subscribed_fulltex