Proefschrift--Universiteit Leiden, 2003. / Notes bibliogr. en fin de chap.

Reproduction de : Thèse de doctorat : Neurosciences pharmacologiques : Metz : 2002. / Titre provenant de l'écran-titre. Notes bibliographiques.

Spexin (SPX), also called neuropeptide Q (NPQ), is a novel neuropeptide discovered recently using the bioinformatic approach. Except for mammals, SPX has not been reported in lower vertebrates including fish and amphibians. Following its discovery, the biological functions of this peptide in both higher and lower vertebrates are still largely unknown. To examine the structure and functions of SPX in fish model, molecular cloning of goldfish SPX has been performed and found to be highly comparable to its mammalian counterparts. In goldfish, broad expression of SPX transcripts has been found in various tissues. In vivo feeding studies have revealed that SPX mRNA levels in the telencephalon, optic tectum and hypothalamus of goldfish brain could be elevated by food intake. Brain injection of goldfish SPX, however, inhibited both basal and NPY- and orexin-induced feeding behaviour and food consumption. Similar treatment has also reduced transcript expression of NPY, AGRP and apelin with concurrent rises in CCK, CART, POMC, MCH and CRH mRNA levels in different brain areas examined. The differential effects of goldfish SPX on NPY, CCK and MCH transcript expression could also be noted in vitro in goldfish brain cell culture. In mice, SPX has been also found to be expressed within the brain-gut axis, including the stomach and specific neuronal subpopulations within the hypothalamus, including the ARC, PVN, DMN, and VMN. Similar to goldfish, feeding has shown to affect SPX mRNA and protein expression. Fasted animals have lower SPX mRNA in the stomach, and lower SPX protein levels in the serum and glandular stomach; the opposite effects have been noted in ad libitumfed animals. Both IP and ICV injection of SPX could produce a short-term feeding inhibitory effect. Furthermore, ICV administration of SPX could also downregulate hypothalamic expression of NPY, NPY5R, AGRP, and GHSR mRNA, and upregulate leptin receptor and MC4R gene expression concurrently. Taken together, these findings suggests that SPX may act as a satiety factor in vertebrate species. Apparently, SPX expression could be induced by feeding and the neuropeptide could act centrally to inhibit feeding by differentially regulating orexigenic and anorexigenic signals within the CNS. / published_or_final_version / Biological Sciences / Master / Master of Philosophy

To investigate the underlying structural features of the neuropeptides α-melanotropin (α-MSH) and substance P (SP), which are responsible for their biological actions, the following study was undertaken. By means of side-chain, fragment and conformational restriction analysis, several α-MSH peptides were prepared by solid-phase synthesis and evaluated by the frog and lizard skin bioassays. Using conformational restriction and fragment methods, several SP peptides were synthesized and examined for biological activity on the guinea-pig isolated ileum, rat brain binding and intrathecal injection assay systems. The results with the new α-MSH analogues show that the histidine-6 side-chain is not needed for signal transduction, but is very important for full potency. The tryptophan-9 side-chain is similarly not needed for signal transduction, but is critically important for full potency. The data also indicate that the positions 6 and 9 side-chains are important for full potency because they likely interact with the melanophore receptor, rather than playing a role in conformationally folding the MSH peptide into a pseudocyclic structure. The results also show that the arginine side-chain at position 8 is not particularly important for signal transduction or full potency, but on the lizard skin bioassay this side-chain is implicated in the previously reported prolongation of Nle⁴, D-Phe⁷-α-MSH. The data provided by the SP peptides suggest that the previously postulated pseudocyclic structure of the 5-11 sequence may not be as fundamental to SP activity as heretofore believed. The data suggest that this type of turn conformation may be important for signal transduction, but is apparently not the only requirement for receptor recognition. Finally, the data show that part of the signal transduction message of SP is contained within the 5-8 region of the peptide, but that most of the receptor recognition elements are probably located outside this sequence.

No description available.

Rhodnius prolixus is a medically-important hemipteran that serves as a vector of Chagas disease. The distribution and physiological effects of three sequence-related neuropeptides, adipokinetic hormone (AKH), corazonin (CRZ) and AKH/corazonin-related peptide (ACP) have been investigated in R. prolixus. Immunohistochemistry revealed that AKH, CRZ and ACP are not co-localized but are found within a different subset of cells and processes within the central nervous system. Physiologically, CRZ significantly increased the heartbeat rate whereas AKH and ACP did not. AKH significantly increased haemolymph lipid levels whereas CRZ and ACP did not. There is no known function for ACP. Preliminary studies indicated that CRZ may be involved in gating of ecdysis.

Rhodnius prolixus is a medically-important hemipteran that serves as a vector of Chagas disease. The distribution and physiological effects of three sequence-related neuropeptides, adipokinetic hormone (AKH), corazonin (CRZ) and AKH/corazonin-related peptide (ACP) have been investigated in R. prolixus. Immunohistochemistry revealed that AKH, CRZ and ACP are not co-localized but are found within a different subset of cells and processes within the central nervous system. Physiologically, CRZ significantly increased the heartbeat rate whereas AKH and ACP did not. AKH significantly increased haemolymph lipid levels whereas CRZ and ACP did not. There is no known function for ACP. Preliminary studies indicated that CRZ may be involved in gating of ecdysis.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Oregon State University, 1990. / Typescript (photocopy). Includes bibliographical references. Also available online.

Thesis (M.S.)--Youngstown State University, 2008. / Includes bibliographical references (leaves 43-51). Also available via the World Wide Web in PDF format.