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Oxytocin (OT) and vasopressin (VP), and all related hormones, consist of nine amino acids with cysteine residues in positions 1 and 6 that form a six-amino acid cyclic part, and of a C-terminal glycine in α-amidated form. These neuropeptides are classified into oxytocin and vasopressin families based on the amino acid residue at position 8. OT-like and VP-like peptides are present in every vertebrate species. These peptides are a very ancient family of hormones having representatives in diverse species of invertebrates. Invertebrates have either a vasopressin-family peptide or an oxytocin-family peptide, whereas bony fishes, the ancestors of land vertebrates, have both isotocin and vasotocin. Presently, two evolutionary structural lineages have been proposed: an isotocin-mesotocin-OT line, associated with reproductive functions, and a vasotocin-VP line participating in water homeostasis. The ancestral gene encoding the precursor protein has been present in the animal genome for a period exceeding 500 million years of evolution. The exceptionally high stability of this structure of nine-amino acid peptides during the entire process of evolution suggests very powerful selective pressure, possibly by evolution together with respective receptors and specific processing enzymes. A novel gene with a distinct function and expression appeared during evolution through duplication of an ancestral gene. The synteny and order of genes in the neurohypophysial hormone gene locus are conserved in the lamprey, elephant shark, coelacanth, and tetrapods, but disrupted in teleost fishes presumably due to the rearrangements facilitated by a whole-genome duplication event in the teleost fish ancestor.
MALDI-TOF/TOF tandem mass spectrometry has been applied to determine the complete sequence of a CAPA-PVK in the Gulf Coast tick, Amblyomma maculatum. Single cell analysis allowed the identification of the amino acid sequence of Ixori-PVK (PALIPFPRV-NH2), a periviscerokinin which had previously been identified from two other ticks, Ixodes ricinus and Boophilus microplus. The identification indicates greater conservation of sequence for the CAPA-PVK/CAP2b family in ticks as compared with insects. Side-chain fragmentation experiments provided data to distinguish between Leu/Ile ambiguities. The tick CAPA peptide shows a high sequence homology with other members of the insect periviscerokinin/ CAP2b peptides, which are associated with the regulation of critical physiological processes such as diuresis. Thus, the identification of this neuropeptide will provide the experimental basis to better understand regulation of water balance in these arthropods, providing a potential opportunity to develop neuropeptide-based control strategies against these livestock pests.
The review presents our results on the regulatory role of prostaglandins (PG) and nitric oxide (NO) in the activation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic, adrenergic and histaminergic systems and by neurohormones: corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) under basal conditions. The synthesis of endogenous PG or NO was inhibited by non-selective and selective cyclooxygenase (COX) antagonists and nitric oxide synthase (NOS) blockers given 15 min before the respective receptor agonist and HPA axis activity was assessed 1 h later by measuring plasma ACTH and serum corticosterone levels. The muscarinic agent - carbachol-induced HPA response was considerably supressed by piroxicam, a predominantly constitutive cyclooxygenase (COX-1) inhibitor and significantly diminished by indomethacin, a non-selective COX blocker, but was unaffected by compound NS-398, an inducible cyclooxygenase (COX-2) antagonist. A non-selective NOS antagonist L-NAME and neuronal NOS blocker L-NNA significantly intensified the carbachol-induced corticosterone secretion. The nicotine-induced increase in ACTH and corticosterone response was significantly supressed by piroxicam, and diminished by indomethacin, but was significantly augmented by L-NAME and L-NNA. The inhibition of PG synthesis by indomethacin totally abolished or reversed the increase of nicotine-induced hormone responses to both NOS blockers. The i.c.v. phenylephrine, an alpha1-adrenergic receptor agonist - evoked HPA response was significantly impaired by piroxicam and compound NS-398 and more potently reduced by L-NAME. The i.c.v. clonidine, an alpha2-adrenergic agonist - elicited HPA response was also considerably decreased by piroxicam, compound NS-398 and L-NAME. By contrast, the stimulatory effect of i.c.v. isoprenaline, a non-selective ß-adrenergic agonist, was not altered by either COX or NOS inhibitors. The i.c.v. histamine- and HTMT, a histamine H1-agonist-induced ACTH and corticosterone response were significantly diminished by piroxicam and indomethacin, respectively. Compound NS-398, did not markedly alter the HPA response to HTMT or amthamine, a histamine H2 receptor agonist. Inhibition of endogenous NO synthesis by a neuronal NOS inhibitor 7-nitroindazole markedly enhanced the histamine-induced hormone secretion, abolished the HTMT-induced response and did not substantially alter the amthamine-evoked ACTH and corticosterone secretion. COX blockers did not significantly affect the CRH-induced HPA response and the inhibition of NO synthesis by L-NNA markedly intensified ACTH response. The vasopressin-stimulated increase in HPA response, was considerably reduced by the inhibition of PG synthesis by both COX antagonists while inhibition of NO synthesis by NOS blockers greatly enhanced this response. The involvement of PG and NO in the neurohormonal regulation of HPA activity depends mainly on greatly complex and tightly regulated mechanisms at the level of second messengers IP3 and adenylyl cyclase systems.
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