Arg-Phe-Amide Related Peptides、RF-Amide相關(guān)肽

Arg-Phe-Amide RFamide Related Peptides

Definition

Neuropeptides with the Arg-Phe-amide motif at their C termini (RFamide peptides) were identified in the brains of several vertebrates, and shown to have important physiological roles in neuroendocrine, behavioral, sensory, and autonomic functions.

Discovery

Price DA, Greenberg MJ in 1977 studied the structure of a molluscan cardioexcitatory neuropeptide. Neuropeptides with Arg-Phe-amide (RFamide) motif at their C termini, which were found in the ganglia of the venus clam, (FMRFamide), have been identified in the brains of several vertebrates and referred to as RFamide peptide(s). A chicken pentapeptide (LPLRFPamide) has also been isolated from its brain. Two pain modulatory neuropeptides [FF and AF], prolactin-releasing peptide (PrRP), gonadotropin- inhibitory hormone,and GH-releasing peptide are also RFamide peptides. To date, these RFamide-peptides have had important physiological roles in neuroendocrine, behavioral, sensory, and autonomic functions. Two PrRPs consisting of 31 amino acids (PrRP31) and 20 amino acids (PrRP20) from bovine hypothalamus extract were potent stimulators of prolactin (PRL) release as an endogenous ligand of an orphan G protein-coupled receptor (hGR3). Immunocytochemical studies showed that, in rat, PrRP cell bodies were located in the brain and hypothalamus, and that their nerve fibers projected into a wide range of areas in the brain 1,2,3.

Structural Characteristics

FMRF-amide-related peptides (FaRPs) are small peptides of 4–18 amino acids with RFamide (arg-phe-NH2) at the C terminus. Neuropeptides with the Arg-Phe-amide motif at their C termini (RFamide peptides) were identified in the brains of several vertebrates. Moriyama S et al., (2007) identified RFamide peptides, which are teleost prolactin-releasing peptide (PrRP) homologs, in the sea lamprey, Petromyzon marinus and characterized their effect on the release of pituitary hormones in vitro. Two RFamide peptides (RFa-A and RFa-B) were isolated from an acid extract of sea lamprey brain, including hypothalamus by Sep-Pak C18 cartridge, affinity chromatography using anti-salmon PrRP serum, and reverse-phase HPLC on an ODS-120T column. Amino acid sequences and mass spectrometric analyses revealed that RFa-A and RFa-B consist of 25  and 20 aa, respectively, and have 75% sequence identity within the C-terminal 20 aa. The RFa-B cDNA encoding a preprohormone of 142 aa was cloned from the lamprey brain, and the deduced aa sequence from positions 48–67 was identical to the sequence of RFa-B  4.

Mode of Action

The potency (muscle force-generated) of a number of long-chain RFamide neuropeptides has been examined. Many of the heptapeptides, octapeptides and the decapeptide LMS were found to induce greater contraction than FMRFamide in both smooth muscles and in both species. RFamide neuropeptides interacted with the neurotransmitter acetylcholine in an additive way and RFamide-induced contractions were inhibited by the neuromodulator serotonin. Pre-treatment with a calcium-free saline completely abolished acetylcholine-induced responses but only partially inhibited RFamide responses in the muscles, suggesting that acetylcholine acts to cause influx of extracellular calcium for contraction. Result suggests that an additional involvement of a fast calcium channel is present in the RFamide responses. Force regulation in these muscles appears to result from a complex interaction of RFamide neuropeptides with the primary transmitter acetylcholine and the neuromodulator serotonin 5.

Unlike in mammals, a few RFamide peptide fibers were projected to the pituitary, and terminated close to PRL producing cells in the rostral pars distalis (RPD) and to the somatolactin somatolactin (SL)-producing cells in the pars intermedia (PI) in rainbow trout. On the basis of the localization of salmon RFamide peptide, compared its hypophysiotropic effects on the release of three evolutionarily related hormones, PRL and SL. Salmon RFamide peptide stimulated PRL release from the pituitary both in vivo and in vitro, as well as in tilapia. Salmon RFamide peptide also affected SL releases from the pituitary  6,7.

Functions

Regulation of PRL release, these results indicate that RFamide peptide is a major hypothalamic peptide involved in the regulation of PRL release and that this peptide may exist throughout vertebrate evolution 6.

RFamide during the development of a primary polyp, antisera to the sequence Arg-Phe-amide (RF-amide) have a high affinity to the nervous system of fixed hydroid polyps. Incubation of Hydractinia echinata gastrozooids with RFamide antisera visualizes an extremely dense plexus of neuronal processes in body and head regions. A ring of sensory cells around the mouth opening is the first group of neurons to show RFamide immunoreactivity during the development of a primary polyp 8.

Two RFamide peptides in lamprey were identified, which are structurally related to teleost PrRP, by peptide isolation and cDNA cloning from lamprey brain/hypothalamus. Evidence suggests that RFamide peptides are major hypothalamic and/or pituitary peptides that may be involved in inhibition of GH and MSH release in lamprey 4.

References

1. Price DA, Greenberg MJ (1977). Structure of a molluscan cardioexcitatory neuropeptide. Science, 197:670–671.

2.  Dockray GJ, Reeve Jr JR, Shively J, Gayton RJ, Barnard CS (1983). A novel active pentapeptide from chicken brain identified by antibodies to FMRFamide. Nature, 305:328-330.

3. Yang HY, Fratta W, Majane EA, Costa E (1985). Isolation, sequencing, synthesis, and pharmacological characterization of two brain neuropeptides that modulate the action of morphine. PNAS., 82:7757-77614.

4. Moriyama S, Kasahara M, Amiya N, Takahashi A, Amano M, Sower SA, Yamamori K, Kawauchi H (2007). RFamide peptides inhibit the expression of melanotropin and growth hormone genes in the pituitary of an Agnathan, the sea lamprey, Petromyzon marinus. Endocrinology, 148(8):3740-3749.

5. Moulis A, Huddart H (2004). RFamide neuropeptide actions on molluscan proboscis smooth muscle: interactions with primary neurotransmitters J Comp Physiol B., 174(5):363-370.

6. Moriyama S, Ito T, Takahashi A, Amano M, Sower SA, Hirano T, Yamamori K, Kawauchi H (2002). A homolog of mammalian PRL-releasing peptide (fish arginyl-phenylalanyl-amide peptide) is a major hypothalamic peptide of PRL release in teleost fish. Endocrinology, 143:2071-2079.

7. Sakamoto T, Agustsson T, Moriyama S, Itoh T, Takahashi A, Kawauchi H, Björnsson BT, Ando M (2003). Intra-arterial injection of prolactin-releasing peptide elevates prolactin gene expression and plasma prolactin levels in rainbow trout. J Comp Physiol., 173:333-337.

8. Grimmelikhuijzen CJP (1985). Antisera to the sequence Arg-Phe-amide visualize neuronal centralization in hydroid polyps. Cell and Tissue Research., 241(1):171-182.