Peptides
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To elucidate roles of microvascular factors in the pathogenesis of renal complications during endotoxemia, that is characterized by renal vasoconstriction and systemic hypotension/generalized non-renal vasodilation, we profile the expression pattern and time-course of three key vaso-regulators, namely endothelin (ET)-1, nitric oxide (NO), and angiotensin II (Ang II). We hypothesize that disruption of the overall balance between vasodilatation and vasoconstriction in the kidney, during the early phase of sepsis, contribute to its (kidney) predisposition to acute renal failure. Adult male Wistar rats were rendered endotoxemic at different time points (1, 3, 6 and 10 h) by a single i.p. injection of lipopolysaccharide (LPS) (15 mg/kg) dissolved in saline. ⋯ Whereas levels of renal NO increased time-dependently following LPS administration, with a 2240-fold increase in renal iNOS expression, levels of eNOS, were almost unchanged. In conclusion, the present study overall reveals intriguing and complex dynamics between levels of vasoconstrictors and vasodilators during the early phase of LPS-induced endotoxemia. These shifts in molecular expressions are likely triggered by compensatory mechanisms aimed at counteracting the undesirable and dominant effects of one group of vaso-regulatory moiety over the other.
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CART peptides are found in brain and spinal cord areas involved in pain transmission. In the present study, we investigated the role of rat CART (55-102) in the modulation of chronic pain using models of chronic neuropathic (nerve injury model) and inflammatory (carrageenan test) pain models in the mouse after intrathecal administration. ⋯ Although CART (55-102) attenuated carrageenan-induced hyperalgesia, it failed to reduce the inflammation associated with this model. These results suggest the involvement of the CART peptides in the development of hyperalgesia and allodynia associated with neuropathic pain.
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A novel 31-residue toxin, named as7a, was isolated and characterized from the venom of Conus austini, a vermivorous cone snail collected in the western Gulf of Mexico. The complete amino acid sequence, TCKQKGEGCSLDVgammaCCSSSCKPGGPLFDFDC, was determined by automatic Edman sequencing after reduction and alkylation. ⋯ The purified peptide elicited toxic effects in the freshwater snail Pomacea paludosa after intramuscular injection, but it had no effect when injected intracerebrally into mice. The structural similarity of peptide as7a to other gamma-conotoxins suggests that modulation of pacemaker channels could be responsible for its biological activity.
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Vasopressin is one of the key regulators of the body's water and solute balance. When this balance is pathologically disturbed, determination of serum vasopressin concentrations might be a helpful tool for guiding therapy. However, due to its instability and considerable association to platelets, reliable measurement of circulating vasopressin is difficult to achieve, if at all. ⋯ Since copeptin is derived from the same precursor peptide as vasopressin, released amounts of copeptin should mirror those of vasopressin. With a newly developed sensitive sandwich immunoassay, we detected strongly elevated concentrations of fully processed copeptin in serum of septic shock patients. The magnitude of elevation and the high stability of copeptin in serum and plasma indicate that copeptin measurement is not affected by the problems, which are associated with the direct measurement of vasopressin, and thus is apparently suitable to indirectly determine the release of vasopressin.
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Review
Urotensin II-related peptide, the endogenous ligand for the urotensin II receptor in the rat brain.
Urotensin II (UII) is a piscine neuropeptide originally isolated from the teleost urophysis. The existence of UII in mammals has been demonstrated by cloning of the mammalian orthologs of UII precursor protein genes. While rat and mouse orthologs have been reported, only the tentative structures of UII peptides of these animals have been demonstrated, since prepro-UII proteins lack the typical processing sites in the amino-terminal region of the mature peptides. ⋯ URP was found to bind and activate the human or rat urotensin II receptors [GPR14, UT receptor (UTR)] and showed a hypotensive effect when administrated to anesthetized rats. The prepro-URP gene is expressed in several rat tissues, although with lower levels than the prepro-UII gene and, in the human, is expressed comparably to prepro-UII in several tissues except the spinal cord. These results suggest that URP is the endogenous and functional ligand for urotensin II receptor in the rat and mouse, and possibly in the human.