Study Of Non-Addictive Analgesic In Agkistrodon Acutus Venom

Pain which is a symptom of many diseases is a protective reaction when bodysuffers noxious stimulation. It also is a subjective feeling mainly composed ofsensory discomfort and corresponding feeling reactions. The long-term misuse ofordinary analgesics can easily result in addiction and tolerance. It is of greatimportance to find new non-addictive analgesic. Snake venoms complicatedmixture secreted by venom gland, made up of kinds of proteins, polytides,enzymes and small molecular substances. Snake venoms have wide biologicalactivities. The use of snake venoms instead of morphia during the late stage ofcancer has been applied. Effective analgesic product has been isolated from Najanaja and it could be the important substitute of morphia because of its higheranalgesic activity and non-addiction. It's a convenient way to screen newanalgesics from snake venoms by using μ opioid receptor of CHO cell. Analgesics can be classified two sorts. Narcosis analgesics(opioids) act onnerve centre appropriately for sharp pain as if Morphine, but NSAIDs play a partin peripheral nerve appropriately for dull pain such as Aspirin. Opioids are nativeopioid alkaloids or their semisynthetic derivatives, which can stimulate opioidreceptors by binding to them. Recently, people cloned four typical opioid receptorsμ, δ ,κ and σ ,and their nucleotide sequence were also determined. Opioidreceptors are coupling with G protein. The message transmission in a cell of theopioid receptors is identical on the whole. The different pharmacological effects ofopioids have something to do with the distribution of their corresponding isoform. 70吉林大学硕士学位论文 英文摘要(ABSTRACT)The endogenous ligands of opioid receptors are mainly composed of theenkaphalin, the endorphin and the dynorphin., which are encoded by various genes.In general, analgesic effect is closely related to μ-receptor ,when injectingMorphine into the mouse with defection of μ-receptor, analgesic effect doesn'thappen. It has been illustrated that analgesic effect will not happen whenδ-receptor is activated. and analgesic effect have not directive relation with δ-receptor and κ-receptor . Therefore, CHO-μ was used to screen new analgesicsfrom snake venom in our study. Cells take in nutrients, typically carbohydrates as glucose, and break themdown to produce useful energy and waste products. The primary waste productsthat are excreted are lactic acid and carbonic acid(carbon dioxide). The rate atwhich cells excrete acids into their environment is very closely linked to the rate atwhich they convert foot to energy, their metabolic rate. Cells respond to aparticular stimulus, for example, a neurotransmitter binding to a cell-surfacereceptor, in complex ways that are reliably reflected in a chang in the cell'smetabolism. Responses to stimuli can be transient or sustained, but the response toa particular stimulus is reproducible under constant conditions. In our study, wescreened stimulus of μ opiod receptor from Agkistrodon acutus venom accordingto their affinity to CHO-μ, through measuring the rate at which CHO cellsacidified their immediate environment, by using the Cytosensor MicrophysiometerSystem. The mouse writhing test (sc. 0.25 mg/kg) proved its higher analgesicactivity. The tail erecting test (sc. 1 mg/kg) and the mouse jumping test (sc. 1mg/kg) proved its non-addiction. Our research implied the feasibility of applyingCHO- μ to discover new non-addictive analgesics. At present, the antinociceptive components discovered from snake venomwere all neurotoxins, which were non-addictive and had no drug dependence . Itsanalgesic effect were stronger than morphine in clinical application. It was 71吉林大学硕士学位论文 英文摘要(ABSTRACT)report...