▎ Dermorphin Ŋuti Numekuku
Nukae nye numekuku si wowɔ tso Dermorphin ŋu?
Nu Gbagbewo Ŋuti Numekuku: Tso ƒe 1970-awo me la, dzɔdzɔmeŋutinunyalawo tsɔ wo ɖokui na be yewoake ɖe nusiwo ŋu ŋutilã ƒe dɔwɔwɔ tɔxɛwo le tso nugbagbewo me. Amewo va kpɔe dze sii vivivi be le nɔnɔmetɔtrɔ ƒe ɖoɖo didi la me la, lãwo awɔ nugbagbevi tɔxɛ vovovowo be woatrɔ ɖe nutoa me ŋu ahalé agbe ƒe dɔwɔnawo me ɖe asi, eye atikewɔmɔnu vevi aɖewo ate ŋu anɔ molecule siawo ŋu.
Nu Siwo Le Tsi Kple Tsi Me Ƒe Ŋutilã Ƒe Tɔxɛ: Dɔ geɖe le lã siwo nɔa tsi kple anyigba me ƒe ŋutigbalẽ ŋu, abe gbɔgbɔ, ametakpɔkpɔ, kple nusiwo dona le eme ene. Tsi kple tsi me lãwo ƒe ŋutigbalẽ ƒe lãkusiwo ate ŋu aɖe nu gbogbo aɖewo siwo wɔa dɔ le nugbagbewo me, siwo wɔa akpa vevi aɖe le ametakpɔkpɔ tso dzɔdzɔmefutɔwo si me kple tɔtrɔ ɖe nutoa me ŋu me. Peptide-nu gbogbo aɖewo le lã siwo nɔa tsi me kple anyigba geɖe ƒe ŋutigbalẽ me, siwo ƒe wɔwɔme le vovovo eye woƒe dɔwɔwɔ le mɔ vovovowo nu, si hea dzɔdzɔmeŋutinunyala geɖe ƒe susu.
Dermorphin si Ŋu Woke Ðe: Le ƒe 1981 me la, Italy dzɔdzɔmeŋutinunyalawo ɖe Dermorphin ɖe vovo tso South America ƒe atiglinyi (Phyllomedusa sauvagii) ƒe ŋutigbalẽ me tsiwo me zi gbãtɔ. To ati ƒe akpɔkplɔ ƒe ŋutigbalẽ me tsiwo ƒe akpawo me dzodzro kple nugbagbewo ƒe dɔwɔwɔwo didi me la, wokpɔe be Dermorphin si le eme la wɔa vevesesenutsitike sesẽ aɖe eye wòlɔ̃a opioid xɔlawo ŋutɔ. Nusi ŋu woke ɖo sia ʋu numekuku ƒe mɔfiame yeye aɖe le vevesesenutsitike ŋu.
Nukae nye Dermorphin ƒe dɔwɔwɔ ƒe mɔnu?
1. Babla ɖe Opioid Xɔlawo ŋu
Dermorphin nye peptide sesẽ aɖe si le abe opioid ene si ate ŋu atiae be wòabla ɖe μ-opioid xɔlawo ŋu. Kpekpeɖeŋu sia naa nusiwo xɔa dɔlékuiwo wɔa dɔ, si wɔnɛ be ŋutilã ƒe dɔwɔwɔ ɖe wo nɔewo yome [1, 2] . Le kpɔɖeŋu me, le dodokpɔ siwo wowɔ le lãwo me me la, eɖe vevesesenutsitike ƒe ŋusẽ sẽŋu aɖe fia [1, 2] . Woate ŋu akpɔ eƒe vevesesenutsitike ƒe ŋusẽ to vevesese ƒe dzesiwo ƒe kaka nu. Ne wotsɔ vevesese ƒe dzesiwo yi ahɔhɔ̃mekawo me la, ana ahɔhɔ̃mekawo nado dzidzɔ na wo ahada tu. Ne Dermorphin bla ɖe μ-opioid xɔla ŋu vɔ la, ate ŋu axe mɔ na ahɔhɔ̃mekawo ƒe dzodzo, si ana vevesese ƒe dzesiwo ƒe kaka dzi naɖe akpɔtɔ.
2. Ŋusẽkpɔɖeamedzi ɖe Lãmetsiŋusẽ Ŋu
Dɔwɔwɔ ɖe ame dzi le Akɔta ƒe Dzidzeme
Le amegbetɔwo ŋuti numekukuwo me la, wokpɔe be dermorphin dodo ɖe ʋuka me ate ŋu ana nociceptive flexor reflex threshold nadzi ɖe edzi ŋutɔ eye wòanɔ anyi ɖaa le lɔlɔ̃nu faa dɔwɔla siwo le lãmesẽ me [2] . Esia ɖee fia be dermorphin ate ŋu axe mɔ ɖe nociceptive signals ƒe kaka nu le aklã ƒe seƒe. Dɔwɔwɔ sia dzena le amesiwo xɔ abi blibo le aklã me atraɖii hã ŋu, si gaɖo kpe edzi be dermorphin koŋ wɔa akpa aɖe le mɔxexe ɖe vevesese ƒe kaka nu le aklã ƒe ɖoɖo nu.
Naloxone ate ŋu atrɔ dermorphin ƒe mɔxexeɖedɔléle nu ƒe ŋusẽkpɔɖeamedzi ɖe nociceptive spinal reflex dzi ƒe akpa aɖe (anɔ abe 50%). Esia ate ŋu afia be dermorphin wɔa dɔ kple aklã me opioid xɔlawo ƒe hatsotso vovovowo be wòawɔ vevesesenutsitike [2]..
Ŋusẽkpɔɖeamedzi ɖe Central Nervous System dzi
DM dodo ɖe ahɔhɔ̃mekawo me naa dɔlélenutsiŋutete ƒe dɔwɔwɔ si nɔa anyi didi [1] . Esia ɖee fia be dermorphin ate ŋu awɔ vevesesenutsitike to dɔwɔwɔ ɖe lãmeka siwo le titina dzi me. Gake womese alesi tututu dermorphin wɔa dɔ le lãmekawo ƒe dɔwɔwɔ me gɔme bliboe haɖe o.
Le avugbɔ̃e dodokpɔwo me la, le dermorphin dodo ɖe ʋuka me megbe la, avugbɔ̃eawo ƒe nuwɔna ɖee fia be ɣeyiɣi si wotsɔ nɔa anyi kpoo eye womeʋãna o dzi ɖe edzi ŋutɔ, eye lɔlɔ̃nu faa dɔwɔnawo dzi ɖe kpɔtɔ, gake mekpɔ ŋusẽ aɖeke ɖe hippocampal electroencephalogram ƒe ɖoɖo kple zi gbɔ zi geɖe dzi o [3] . Esia fia be dermorphin ate ŋu akpɔ ŋusẽ ɖe nuwɔna aɖewo koŋ kple lãmekawo ƒe akpa aɖewo dzi.
3. Ŋusẽkpɔɖeamedzi ɖe Dɔgbo ƒe Mɔka Dzi
Dermorphin kpɔa ŋusẽ ɖe dɔgboa ƒe ʋuʋu dzi le sisiblisiwo me. Ne wotsɔe sɔ kple morphine la, dermorphin dodo ɖe ahɔhɔ̃mekawo me xea mɔ na dɔgboa ƒe ʋuʋu abe morphine ene, eye eƒe dɔwɔwɔ nye morphine tɔ zi gbɔ zi 143 [4] . Dɔ si naloxone wɔna ɖe dermorphin dzi si tsi tre ɖe eŋu la mewɔa dɔ boo o wu esi wòkpɔna ɖe morphine dzi. Naloxone si wotsɔ ƒo ƒu ɖe ahɔhɔ̃mekawo me ate ŋu atsi tre ɖe ŋusẽ si dermorphin si le ahɔhɔ̃mekawo me kpɔna ɖe dɔgboa dzi ŋu, evɔ atike si wodona ɖe dɔgboa me ya wɔa dɔ le agbɔsɔsɔ si nye 8mg/kg me ko. Dermorphin si wodona ɖe dɔgboa me mewɔa dɔ kura le agbɔsɔsɔ si wɔa dɔ wu (microgram 0.56 le sisiblisi ɖeka me) me o. Dermorphin dodo ɖe dɔgboa me ƒe agbɔsɔsɔme dzi ɖeɖe kpɔtɔ (tso microgram 12 va ɖo 6400 le kilogram ɖeka me) kpɔa ŋusẽ si xea mɔ na dɔgboa ƒe ʋuʋu si le eɖokui si le agbɔsɔsɔa me, gake mewua 50% gbeɖe o. Naloxone ƒe agbɔsɔsɔ gã (30mg/kg, atike si wodona ɖe dɔgboa me) koe ate ŋu atsi tre ɖe atike sia dodo ɖe dɔgboa me ƒe ŋusẽkpɔɖeamedzi ŋu. Esia ɖee fia be ŋusẽ si dermorphin kpɔna ɖe dɔgboa dzi ate ŋu alɔ akpa siwo le titina kple esiwo le gota siaa ɖe eme.
4. Ŋusẽkpɔɖeamedzi ɖe Lãmetsiwo Dzi
Wosrɔ̃ nu tso dermorphin ƒe dɔwɔwɔ ŋu le akpɔkplɔ ƒe dɔgbo ƒe lãmeka ƒe cross-section strip to mechanographic recorder dzi [5] . Numekukua me tsonu ɖee fia be dermorphin (10 (-5)-10 (-8) M) ate ŋu axe mɔ na acetylcholine ƒe dɔwɔwɔ, dɔwɔwɔ le eɖokui si, kple lãmekawo ƒe tete si elektrikŋusẽ ƒe ʋuʋu tẽ hena vɛ. Esesẽna be woatrɔ ŋusẽkpɔɖeamedzi siawo katã. Ne wodo dermorphin ɖe nusi wotsɔ dea lãmekaa me le lãmekaa ƒe K (+) depolarization (KCl - 100mM) me la, mate ŋu axe mɔ ɖe dɔwɔwɔ siwo dzɔna le wo ɖokui si kple esiwo wodona ɖa nu o. Eyata dermorphin kpɔa ŋusẽ ɖe elektrikŋusẽ dzi eye ate ŋu awɔ dɔ ɖe lãmeka ƒe lãmenugbagbeviwo ƒe lãkusi ƒe Ca (2+) mɔ siwo nɔa te ɖe elektrikŋusẽ dzi dzi.
5. Ƒomedodo si le Molekyulãwo ƒe Dɔwɔɖoɖo Kple Dɔwɔwɔ ƒe Mɔnu dome
Wowɔ molecule mɔ̃ɖaŋununya ƒe nɔnɔmetatawo le dermorphin dzi (Pattabiraman N, 1986). Numekukua ɖee fia be D-Ala2 si le N-nuwuƒe kple L-Pro6 ƒe susɔe si le C-nuwuƒe le dermorphin ƒe ɖoɖoa me ɖee fia be β-trɔtrɔ ate ŋu anɔ anyi. Le stereochemical ƒe nukpɔsusu nu la, β-trɔtrɔ ƒomevi etɔ̃ (II’, III’, kple V’) ate ŋu anɔ peptide la ƒe N-nuwuƒe, eye β-trɔtrɔ ƒomevi eve (I kple III) ate ŋu anɔ C-nuwuƒe. Le molecule mechanics ƒe akɔntabubuwo me la, wobu conformations ade siwo woxatsa kple conformation ɖeka si keke ta be woatsɔ ada dermorphin ƒe liƒo si sɔ gbɔ kpɔ. Le wo dome la, ŋusẽ si le nɔnɔme etɔ̃ siwo wobla ɖe wo nɔewo ŋu la le ʋɛ wu eye nɔnɔme siwo gbɔna le wo si le goawo katã me: ŋusẽ si sɔ, haidrodzin ƒe kadodo etɔ̃, β-sheet kakɛ si sesẽ afã kple afã, kple Tyr1-Tyr5 ƒe kadodo nyui. β-sheet ƒe wɔwɔme ƒe anyinɔnɔ ate ŋu awɔ akpa aɖe le tiatiawɔblɔɖe ƒe kadodo si le dermorphin kple μ-xɔla dome me.
Nukae nye Dermorphin zazã?
Wozãe hena vevesese dzi kpɔkpɔ le dɔwɔwɔ vɔ megbe: Numekuku aɖe si wowɔ le vome, si me wozã atike si wotsɔ ɖɔa amee le le ƒe 1985 me ɖee fia be Dermorphin si wodo na ame to mɔ si wotsɔ dea ʋuka me dzi la wɔa dɔ ŋutɔ wu atike si wotsɔ ɖɔa amee kple morphine si wotsɔ wɔa dɔe le vevesese dzi ɖuɖu me [6, 7] . Esia ɖee fia be ŋutete gã aɖe ate ŋu anɔ Dermorphin ŋu le dɔwɔwɔ vɔ megbe vevesese dzi ɖeɖe kpɔtɔ me. Le dɔnɔ siwo wowɔ dɔ na le dɔwɔwɔ vɔ megbe gome la, menye ɖeko vevesese dzi kpɔkpɔ nyuie ate ŋu ana dɔnɔwo ƒe akɔfafa nanyo ɖe edzi ko o, ke ate ŋu akpe ɖe dɔnɔwo ŋu woahaya eye woatrɔ ayi agbe si sɔ me hã.
Dɔwɔwɔ le vevesesenutsitike me: Esi wobu eƒe vevesesenutsitike ƒe ŋusẽkpɔɖeamedzi nyui ŋu ta la, wodo susua ɖa hã be woazãe le dɔnɔ siwo de ŋgɔ ƒe vevesesenutsitike me [6, 7] . Le dɔnɔwo ƒe vevesese dzi ɖeɖe kpɔtɔ me la, dɔnɔwo ƒe vevesese dzi ɖeɖe kpɔtɔ nye taɖodzinu vevi aɖe, eye Dermorphin, si ƒe vevesesenutsitike sẽŋu kple eƒe nugbegblẽ le ame ŋu ƒe afɔku si mebɔ boo o ta la, nye tiatia si woate ŋu azã atsɔ aɖe dɔnɔ siwo de ŋgɔ ƒe vevesese dzi akpɔtɔ.
Ŋusẽkpɔɖeamedzi si xea mɔ na aklã ƒe vevesese: Numekukuwo ɖee fia be Dermorphin ate ŋu axe mɔ ɖe nociception ƒe kaka nu le aklã me. Le lɔlɔ̃nu faa dɔwɔla siwo le lãmesẽ me gome la, Dermorphin 0.16mg/kg dodo ɖe ʋuka me ate ŋu ana nociceptive flexor reflex ƒe dzidzenu nadzi ɖe edzi ŋutɔ eye wòanɔ anyi ɖaa [8] . Wokpɔ ŋusẽ ma tɔgbe le amesiwo xɔ abi blibo le aklã me hã ŋu, si ɖee fia be Dermorphin wɔa dɔ le aklã ƒe seƒe koŋ be wòaxe mɔ ɖe vevesese ƒe kaka nu. Ŋusẽkpɔɖeamedzi sia si xea mɔ na aklã ƒe vevesese la naa mɔkpɔkpɔ yeye le dɔnɔ siwo ŋu vevesesedɔ siwo do ƒome kple aklã me dɔlékuiwo le la dada me.
Le nyataƒoƒo me la, Dermorphin nye peptide sesẽ aɖe si le abe opioid ene si ate ŋu abla ɖe μ-opioid xɔlawo ŋu, si ɖea vevesesenutsitike ƒe ŋusẽkpɔɖeamedzi ɖedzesi aɖe fiana eye wòxea mɔ na vevesesenutsitike ƒe dzesiwo ƒe kaka le aklã me. Woate ŋu azãe le vevesesenutsitike le dɔwɔwɔ vɔ megbe, vevesesenutsitike, kple bubuawo me, si hea susu yeyewo vɛ na vevesesenutsitike.
Le Agbalẽŋlɔla La Ŋu
Nusiwo míeyɔ ɖe etame la katã nye esiwo ŋu Cocer Peptides wɔ numekuku le, trɔ asi le wo ŋu eye woƒo wo nu ƒu.
Dzɔdzɔmeŋutinunya ƒe Agbalẽŋlɔla
Giuliano Fontani nye numekula si do ƒome kple Siena Yunivɛsiti, Italy, eye wòléa fɔ ɖe ahɔhɔ̃ŋutinunya kple ŋutilãŋutinunya ŋu. Esrɔ̃ nu tso ŋusẽ si dermorphin, si nye peptide si le dzɔdzɔme nu, kpɔna ɖe nuwɔna kple hippocampal elektrikŋusẽ ƒe dɔwɔwɔ dzi le avugbɔ̃ewo me ŋu, si wɔe be wose opioid xɔlawo ƒe dɔwɔwɔ gɔme. Eƒe dɔa ku ƒomedodo si le ahɔhɔ̃ ƒe dɔwɔwɔ kple nuwɔna dome hã me, eye wòtae ɖe magazinewo abe Agbeŋutinunya ene me. Woŋlɔ Giuliano Fontani ŋkɔ ɖe nyayɔyɔ ƒe nyatakaka me [3].
