1 The release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from the dorsal horn of the rat spinal cord in vitro in response to dorsal root stimulation was measured by radioimmunoassay.2 Stimulation of the dorsal roots (3 or 4 roots on each side) at 10 Hz for 5 min evoked a mean release (RI) of 134.3 ± 17.5 (n = 10) fmol CGRP-LI; the release (R2) evoked by a second stimulation period 30 min later under control conditions was 77 ± 10% (n = 10) of RI. Test compounds were applied to the preparation following release RI, and their effect calculated from the value of R2/R,. 3 Bradykinin (0.01-10 pM) had no significant effect on the basal release of CGRP-LI, but at 0.1-10MM it increased 2-3 fold the release evoked by dorsal root stimulation.4 This effect of bradykinin was prevented by indomethacin (10 pM), or by the B2-receptor antagonist, Hoel40 (1-1I0 M). In the presence of Hoel40, bradykinin significantly reduced R2/R,; the explanation for this is not clear.5 The B,-receptor agonist, Des-Arg-bradykinin (1OMM), did not affect CGRP-LI release nor was the effect of bradykinin blocked by the B,-receptor antagonist, Des-Arg9-Leu8-bradykinin (10MM). 6 Various prostaglandins were found to mimic the effect of bradykinin on CGRP-LI release. Their approximate order of potency was prostaglandin D2 (PGD2) = PGE, > PGF2. = PGE2; PGI2 was ineffective at 1O MM.7 Forskolin (30 MM) and 3-isobutyl l-methylxanthine (IBMX; 10 fM) also increased the evoked release of CGRP-LI. 8 It is concluded that bradykinin acts on B2-receptors in the spinal cord, causing the formation of prostanoids, which in turn cause an enhancement of neuropeptide release from primary afferent nerve terminals in the dorsal horn. This effect may be secondary to activation of adenylate cyclase. Because B2-receptors are mainly associated with primary afferent nerve terminals, it is likely that prostanoid production is also a function of these structures. Whether this action of bradykinin has any physiological function in nociceptive transmission remains unclear.

Purpose The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. Methods Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmissionaggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. Results Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. Conclusions SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. KeywordsCarnosine . Acetylsalicylic acid . Salicylic acid . Antioxidant . Antiplatelet action . Gastrointestinal ulcer Abbreviations ASA acetylsalicylic acid CL chemiluminescence COX cyclooxygenase HPLC high performance liquid chromatography HRMS high resolution mass spectrometry LP lipoproteins LPO lipid peroxidation NBT nitroblue tetrazolium NSAIDs non-steroidal anti-inflammatory drugs

Semax (100 microM) and its Pro-Gly-Pro fragment (20 and 100 microM) delayed the development of calcium dysregulation and reduction of the mitochondrial potential in cultured cerebellar granule cells under conditions of glutamate neurotoxicity. Incubation with these peptides improved neuronal survival by on average 30%. The neuroprotective effect of semax in cerebral ischemia/hypoxia can be due to improvement of mitochondrial resistance to "calcium" stress.

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