Peptides
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Intraperitoneal administration of dermorphin caused dose-dependent changes in rats core temperature and tail skin temperature (indicative of compensatory thermoregulatory vasoreactions in rats). The character of these changes depended strongly on the environmental temperature at which the inversion of the dermorphin-induced thermoregulatory effect was observed. In the cold environment (4-7 degrees C) dermorphin caused a significant, stable, dose-dependent hypothermia. ⋯ Dermorphin-induced changes in tail skin temperature indicate that dermorphin suppresses the thermoregulatory peripheral compensatory vasomotor reactions. Pretreatment with naloxone attenuated dermorphin-induced effects on core temperature and partially enhanced vasomotor effects of dermorphin. The data obtained indicate that dermorphin affects the core temperature regulation via mu-opiate receptors, whereas vasomotor effects of the peptide are probably mediated via naloxone-insensitive receptors.
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Comparative Study
Effects of captopril and Icatibant on bradykinin (BK) and des [Arg9] BK in carrageenan-induced edema.
The effects of captopril, an angiotensin-converting enzyme inhibitor (ACEI), and a selective B2 kinin receptor antagonist (Icatibant) were examined on the paw edema and tissue contents of bradykinin (BK) and des[Arg9]BK following the intraplantar injection of carrageenan in rats. To this end, BK-like immunoreactivity (BK-LI) and des[Arg9]BK-LI were measured with highly sensitive and specific chemiluminescent enzyme immunoassays. Because pentobarbital significantly reduced the carrageenan-induced edema between 3 and 8 h, experiments were conducted in conscious rats. ⋯ It is concluded that inhibition of ACE by captopril enhanced the early production of endogenous BK and the edema formation induced by carrageenan through a B2 receptor-mediated mechanism. However, the B2 receptor does not appear to be involved in the late phase of the inflammatory response (from 5 to 24 h) to carrageenan in rats pretreated with ACEI. Although the concentrations of des[Arg9]BK were greater than those of BK, it is unlikely that B1 receptors play a significant role in this model of carrageenan-induced edema.
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The occurrence of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed in the ankle joints and dorsal root ganglia (L2-L6) by immunohistochemistry and radioimmunoassay (RIA) after unilateral sciatic nerve section in adjuvant arthritis. Nerve section in arthritic rats had no clear-cut effect on warmth, redness, and swelling of ankle joints, but significantly affected the occurrence of SP and CGRP. Immunohistochemical analysis showed an almost complete disappearance of SP-positive fibers in the ipsilateral ankle joint in normal rats after axotomy, whereas in arthritic rats occasional SP-positive fibers remained. ⋯ In dorsal root ganglia, the decrease in SP after surgical denervation was 25% in normal rats and 54% in arthritic rats; the decrease in CGRP was 18% and 27%, respectively. The tissue concentrations of SP and CGRP in ipsilateral ankle joints and dorsal root ganglia were consistently correlated in normal as well as arthritic rats. The present study shows that an interruption of the nerve supply to joints cannot fully prevent the development of arthritis, although it significantly reduces the occurrence of sensory neuropeptides.
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Neuropeptide Y (NPY)-like immunoreactivity (IR) was observed in 20-30% of ipsilateral dorsal root ganglion (DRG) neurons (L4-5) after unilateral transection of rat sciatic nerve. Most of these neurons contained 200 kDa subunit of neurofilaments and galanin. Immunohistochemical analysis combined with retrograde tracing method demonstrated that NPY-IR was detected in cutaneous and muscular sensory, but not in visceral sensory neurons. These findings suggest that NPY coexists with galanin in injured large type A cells, which may innervate the mechanoreceptors in the skin and muscle, such as corpuscles of Meissner and Pacini, or muscle spindles.
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Comparative Study
Characterization of endozepine-related peptides in the central nervous system and in peripheral tissues of the rat.
Endozepines represent a novel family of regulatory peptides that have been isolated by their ability to displace benzodiazepines from their binding sites. All endozepines derive from an 86 amino acid precursor polypeptide called diazepam binding inhibitor (DBI), which generates, through proteolytic cleavage, several biologically active endozepines. The aim of the present study was to compare the molecular forms of endozepines present in different regions of the rat brain and in various peripheral organs using an antiserum raised against the central (biologically active) region of DBI. ⋯ Western blotting analysis of cerebral cortex extracts confirmed the existence of two immunoreactive species with apparent molecular weights 4000 and 6000 Da, which respectively correspond to peaks I and II. Tryptic digestion of peaks I and II generated a single immunoreactive peptide that coeluted with the synthetic octadecaneuropeptide ODN [DBI(33-50)]. These results show that, in different parts of the brain and in various peripheral organs, DBI is rapidly processed to generate two peptides of apparent molecular weight of 4000 and 6000 Da, which both possess the biologically active determinant of endozepines.