1. Spinal release of immunoreactive dynorphin A(1-8) with the development of peripheral inflammation in the rat
A W Duggan, Z Q Zhao, R C Riley Brain Res . 1996 Feb 26;710(1-2):131-42. doi: 10.1016/0006-8993(95)01394-6.
Microprobes bearing immobilised antibodies to dynorphin A(1-8) were used to study the basal and evoked release of this prodynorphin derived peptide in the spinal cord of urethane anaesthetised normal rats and those with a peripheral inflammation. In the absence of any active peripheral stimulus the antibody microprobes detected immunoreactive (ir)-dynorphin A(1-8) in two areas (lamina I and laminae IV-V) in the dorsal horn of the spinal cord of normal rats. With the development of unilateral ankle inflammation over 3 to 5 days following subcutaneous injections of Freund's complete adjuvant, a basal presence of ir-dynorphin A(1-8) was found in both the dorsal and ventral horn regions of both sides of the spinal cord. Lateral compression of the ankles of the normal animals did not release ir-dynorphin A(1-8) during the period of stimulation, but this neuropeptide was detected in increased amounts in the ventral horn following the stimulus. By contrast, compression of inflamed ankles produced elevated levels of ir-dynorphin A(1-8) during the period of stimulus application at three major sites in the ipsilateral spinal grey matter. The largest peak was in the deep dorsal horn/upper ventral horn (laminae VI-VII), with further sites of significant release in the mid dorsal horn (laminae II-V) and the lower ventral horn. The observation that ir-dynorphin A(1-8) is physiologically released in the ventral and deep dorsal in addition to the superficial dorsal horn of the rat suggests an involvement of dynorphins in several aspects of spinal function.
2. Dynorphin A (1-8) inhibits oxidative stress and apoptosis in MCAO rats, affording neuroprotection through NMDA receptor and κ-opioid receptor channels
Shuang Du, Jiaxin Fan, Xiaodong Zhang, Qingling Yao, Shuyin Ma, Meijuan Zhang, Yuxuan Cheng, Shuqin Zhan, Jinming Shi, Huiyang Qu, Mengying Chen, Hong Sun Neuropeptides . 2021 Oct;89:102182. doi: 10.1016/j.npep.2021.102182.
The contents of Dynorphin A(1-8) decreased gradually in ischemic cortices in rats and an intracerebroventricular administration of synthetic Dynorphin A(1-8) reduced the volume of cerebral infarction in our previous research. However, the specific protective mechanism is unclear and Dynorphin A(1-8) is unlikely to cross the blood-brain barrier (BBB) by noninvasive oral or intravenous administration as a macromolecule neuropeptide. In this study, intranasal administration was used to middle cerebral artery occlusion(MCAO) rats to assessed the therapeutic effects of Dynorphin A(1-8) by evaluating behavior, volume of cerebral infarct, cerebral edema ratio, histological observation. Then apoptosis neuron rate was detected by TUNEL staining. Immunohistochemical staining was carried out to explore the alteration of Bcl-2, Bax and Caspase-3. Finally, κ-opioid receptor antagonist and N-methyl-d-aspartate(NMDA) receptor antagonist were used to explore its possible mechanism. We found that MCAO rats under intranasal administration of Dynorphin A(1-8) showed better behavioral improvement, higher extent of Bcl-2, activity of SOD along with much lower level of infarction volume, brain water content, number of cell apoptosis, extent of Bax and Caspase-3, and concentration of MDA compared with those in MCAO model group and intravenous Dynorphin A(1-8) group. Administration of nor-BNI or MK-801 reversed these neuroprotective effects of intranasal Dynorphin A(1-8). In summary, Dynorphin A(1-8), with advantages of intranasal administration, could be effectively delivered to central nervous system(CNS). Dynorphin A(1-8) inhibited oxidative stress and apoptosis against cerebral ischemia/reperfusion injury, affording neuroprotection through NMDA receptor and κ-opioid receptor channels.
3. Lithium increases dynorphin A(1-8) and prodynorphin mRNA levels in the basal ganglia of rats
L Calvetta, J Douglass, K Takeuchi, S P Sivam, O Civelli, J F McGinty, S Li, J S Hong, E Herbert Brain Res . 1988 Apr;427(2):155-63. doi: 10.1016/0169-328x(88)90061-7.
The aim of this study was to understand the possible influence of the antimanic drug, lithium, and the neuroleptic, haloperidol, alone or in combination, on the regulation of dynorphin biosynthesis in the striatum. The study was done using male Fisher-344 rats subjected to a regimen of subchronic administration of lithium chloride (4 mEq/kg/day for 1,2,4 or 6 days, i.p.) or a regimen of chronic oral administration of a diet containing lithium carbonate (1.5 g/kg of the diet). Subchronic administration of lithium increased striatal dynorphin A(1-8)-like immunoreactivity (DN-LI) in a time-related fashion. Immunocytochemistry revealed an increase in DN-LI in fibers and cells clustered in 'patches' throughout striatum. The increase in DN-LI was reversible on cessation of lithium administration. Concurrent administration of lithium and an opiate antagonist, naltrexone, or a dopamine receptor antagonist, haloperidol, did not influence the changes induced by lithium. Chronic oral administration of lithium for 21 days led to an increase in DN-LI in the striatum. Co-administration of haloperidol with the 21 day regimen of lithium administration failed to affect the increase in DN-LI. The prodynorphin mRNA abundance in the striatum was quantitated by a molecular hybridization procedure using a prodynorphin 32P-cRNA probe generated from the Riboprobe system. Evidence from the Northern blot analysis reveals that lithium increases the prodynorphin mRNA abundance in the striatum. These results indicate that lithium affects the dynamics of prodynorphin biosynthesis in the striatum, presumably increasing transcription and/or translational processes.
