Neuropeptides invertebrate

The literature contains numerous references to the use of MS/MS in the determination of new neuropeptides in identified cells of invertebrates (Bulau et al., 2004, for a recent example) and this technique is now being applied to in situ analysis of vertebrate tissues (Fournier et al., 2003). MS/MS is also used for studies of neuropeptide processing (Nilsson et al., 2001), pharmacokinetics of synthetic peptides (Mock et al., 2002), nonpeptide drug metabolism (Kamel et al., 2003), identification of peptides purified by immunoaffinity (Suresh Babu et al., 2004), and MALDI/MS/MS techniques adaptable to brain dialysis (Bogan and Agnes, 2004). 

The invertebrate peptides PCH (pigment-concentrating hormone 46) and AKH I (adipokinetic hormone 47) were the first neuropeptides from invertebrates to have their structure and synthesis described by L. Josefsson in 1983 94). 

Numerous tests carried out in insects with antibodies raised against mammalian neuropeptides revealed reaction products within and outside of the nervous system. Conversely, certain neuropeptides first identified in invertebrates were shown to occur also in mammals and other vertebrates. These commonalities are indicative of a long evolutionary history, as well as a wide distribution of active neuropeptides in neural and non-neural tissues. One of the new insights gained from the use of multiple antisera and carefully conducted specificity tests was the immunocytochemical detection in the insect brain of molecules closely resembling mammalian ACTH, prolactin, and insulin,. The localization of these substances suggests a neurotransmitterlike or neuromodulatory rather than a hormonal role. 

Among recent developments in the elucidation of neuropeptide activities in non-neuronal tissues and cells, those in the immune system are receiving the greatest attention. Fascinating results obtained in invertebrates are in line with those in mammals. 

Neuroendocrine control of invertebrate development was first demonstrated by Kopec CL2) with neck ligation and brain extirpation-reimplantation studies using the gypsy moth, Lymantria dispar (Lepidoptera Lymantriidae). His demonstration of a "pupation factor", origmating in the bi in, provided the impetus for identification of numerous invertebrate physiological processes controlled by peptide neurohormones (3.41 In insects, identified processes now number over thirty (5). Knowledge of these processes has provided for the development of bioassays used in the isolation of neuropeptides. Since 1975, over fo insect peptide neurohormones have been isolated and sequenced (5-81... 

Additional myotropic/inhibitory neuropeptide structures will be characterized on the basis of immunological similarity to vertebrate and invertebrate peptide structures, and also with the techniques of molecular biology. Two initial successes with those methods are discussed in this report (17,25). In addition, antibodies raised against FMRFamide were used to isolate and structurally characterize a nonapeptide containing C-terminal FMRFamide from head extracts of Drosophila (26). Subsequently, the gene that codes for this nonapeptide and eight other FMRFamide-related structures was isolated and sequenced (27,28). 

Figure 3. Schematic diagram of structural relationships between vertebrate and invertebrate neuropeptides discussed in the text. The similarity in sequences suggests that they may have been derived from a common ancestral source.

Arthur S. Edison obtained a B.S. in chemistry from the University of Utah, where he studied monoterpenes isolated from southern Utah sagebrush by NMR. He completed his Ph.D. in biophysics from the University of Wisconsin, Madison, where he developed and applied NMR methods for peptide and protein structural studies under the supervision of John Markley and Frank Weinhold. In 1993, Dr. Edison joined the laboratory of Anthony O. W. Stretton at the University of Wisconsin as a Jane Coffin Childs postdoctoral fellow where he investigated the role of neuropeptides in the nervous system of the parasitic nematode Ascaris suum. He joined the faculty at the University of Florida and the National High Magnetic Field Laboratory in 1996 and is currently the Director of Chemistry Biology at the NHMFL. Dr. Edison s current research is in technology development for high-sensitivity NMR and natural product discovery in nematodes and other invertebrates. Dr. Edison is the recipient of the 1997 American Heart Association Robert J. Boucek Award, a CAREER Award from the National Science Foundation in 1999, and, with his postdoctoral scientist Aaron Dossey, the Beal award for the best publication of the year in the Journal of Natural Products in 2007. 

The conorfamides, isolated from Conus spurius, belong to the RFamide neuropeptide family and may act as an agonist of the FMRF-amide-gated ion channels. In invertebrates, this peptide family has many diverse functions, whereas in the mammalian system they moderate opioid function in the CNS, modulate epithelial Na" " channels, have important cardiovascular effects, and stimulate pancreatic somatostatin secretion. ... 

Structure-activity studies are an indirect method to investigate a possible interaction of AKH peptides with their receptor proteins. For various members of the AKH family a vast body of literature has accumulated, employing bioassays such as lipid mobilization in locusts and the tobacco hommoth Manduca sexta, carbohydrate mobilization in various cockroach species, the activation of phosphorylase in the larvae of M. sexta, or the inhibition of fatty acid synthesis in the fat body of locusts [10, 33, 37, 53]. Contrary to most other invertebrate neuropeptides, the insect members of the AKH family do not have a core sequence which is essential for potency, however, the N-terminal pGlu residue and the C-terminal amide are important, as well as the aromatics at position 4 and 8. To achieve full efficacy, all amino acids are apparently important. There is also no superagonist found and also no inhibitor. 

There is a very diverse superfamily of neuropeptides present in most invertebrates that are called FMRFamide-related peptides (FaRPs) the name is based on the first member of this group isolated from ganglia of a clam (mollusc) and identified as Phe-Met-Arg-Phe amide (FMRFamide) this peptide had a strong cardioexcitatory action [185]. A number of important families are grouped into this superfamily the FMRFamides and extended FMRFamides, myosuppressins (FLRFamides), sulfakinins (HMRFamides) and, neuropeptides F and Y (NPFs and NPYs). 

Of the antisera tested so far, those with the widest immunoreactivity across species and most commonly associated with neuromuscular locations (proximity of neurites to muscle) include pancreatic polypeptide-like peptide(s) (PP) of the neuropeptide Y (NPY) superfamily and Phe-Met-Arg-Phe-amide (FMRFamide)-like peptide(s), an invertebrate family of neuropeptides (22, 53, 55, 57, 61, 82, 89-92, 95, 103). In parasitic flatworms immunoreactivities to members of the NPY superfamily (neuropeptide Y, peptide YY and pancreatic polypeptide) and FMRFamide are likely to be largely or completely due to the native neuropeptide F (NPF) (22, 93, 100, 101). This 39 amino acid neuropeptide was first isolated and sequenced from the cestode Moniezia expansa and is viewed as a closely related member of the NPY superfamily it represents the first invertebrate member of this family to be isolated and sequenced. Similar staining patterns for the PP and PYY members of the NPY superfamily, FMRFamide and NPF have been obtained. Ultrastructural studies have co-localized NPF, PP and FMRFamide to a specific population of large dense-core vesicles in neurons of some species. NPF quenches PP and FMRFamide immunoreactivities but not vice versa. These results obtained in species of trematodes and cestodes suggest that most, if not all, of the... 

Gustafsson, M. K. S. and Wikgren, M. C. (1989) Development of immunoreactivity to the invertebrate neuropeptide small cardiac peptide B in the tapeworm Diphyllobothrium dendriticum. Parasitol. Res. 75 396-400. 

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