Bya Cocer Peptides 
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EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Melanotan-II Okukubaganya ebirowoozo
Melanotan-II (MT-II) ye α-melanocyte-stimulating hormone (α-MSH) analog ekoleddwa mu kibinja ky’ebirungo ebiziyiza melanocortin. MT-II tekozesebwa mu mirimu gyokka egyekuusa ku kulongoosa; mu by’okunoonyereza ku by’obusawo, kinoonyezebwa okulaba oba kiyinza okukozesebwa mu kujjanjaba embeera ng’obuzibu bw’okusituka.
Ekifaananyi 1 Ensengekera ya Melanotan-II.
Enkola ya Melanotan-II ey’Ekikolwa
MT-II okusinga ekola ebikolwa byayo nga ekwatagana n’ebikwata melanocortin (MCRs). Famire y’ebikwata melanocortin erimu ebika ebitonotono ebingi nga MC1R, MC2R, MC3R, MC4R, ne MC5R. MT-II ye non-selective melanocortin receptor agonist esobola okwesiba n’okukola MCR eziwera.
Mu lususu, MT-II yeekwata ku MC1R ku ngulu kwa melanocytes, n’ekola adenylate cyclase, eyongera ku miwendo gya cyclic AMP (cAMP), bwe kityo n’ekola protein kinase A (PKA). PKA ekola ekirungo ekikwata ku microphthalmia-associated transcription factor (MITF) okuyita mu phosphorylation. MITF is a key transcription factor in melanin synthesis, Etereeza okwolesebwa kw’obuzaale nga tyrosinase, tyrosinase-related protein-1 (TRP-1), ne tyrosinase-related protein-2 (TRP-2), nga zino ze enzymes ezikwatibwako mu kukola melanin, okukkakkana nga ziviirako okweyongera mu langi y’olususu n’okutuuka ku tanning effect.
Mu nkola y’obusimu, MT-II nayo ekwata ku nkola ezimu ez’obusimu. Kiyinza okusitula enkola ya oxytocin ey’omu makkati. Okunoonyereza kulaga nti okukuba empiso ya MT-II mu misuwa kireetera nnyo okwolesebwa kwa Fos mu busimu obunene obwa suprachiasmatic nucleus (SON) ne paraventricular nucleus (PVN) obwa hypothalamus, okuddamu okuyinza okukendeezebwa nga tebannaba kukuba mpiso ya melanocortin antagonist SHU-9119 mu bwongo. Ebiwandiiko ebikwata ku masanyalaze biraga nti okukuba empiso ya MT-II mu misuwa kyongera ku mirundi gy’okukuba kw’obusimu bwa oxytocin mu SON naye tekivaako kufulumya dendritic oxytocin munda mu SON. Olw’okunoonyereza okwakolebwa emabegako okulaga nti okukozesa obutereevu eddagala lya melanocortin agonists kiziyiza obusimu obuyitibwa supraoptic nucleus (SON) oxytocin neurons, ebiva mu MT-II eyingizibwa mu misuwa waakiri biyinza okuba nga bitabaganyizibwa waakiri ekitundu mu ngeri etali butereevu, ekiyinza okuyita mu kukola ebiyingizibwa okuva mu kikolo ky’obwongo eky’omugongo, nga MT-II nayo eyongera ku kwolesebwa kwa Fos.
Okugatta ku ekyo, MT-II erina enkola ezimu ez’okukola ku nkyukakyuka y’amasoboza n’okutereeza ebbugumu. Mu kugezesa kw’ebibe, okukuba empiso ya MT-II mu lubuto kuleeta hypometabolism/hypothermia ey’amaanyi era ey’akaseera obuseera. Ekintu kino eky’okukendeera kw’ebbugumu kibula mu mbeba za Kit W-sh/W-sh ezibulamu obutoffaali obuyitibwa mast cells, ekiraga nti obutoffaali obuyitibwa mast cells bwetaagisa nnyo eri MT-II-induced hypothermia. MT-II esobola okusitula obutoffaali obuyitibwa mast cells okuyita mu nkola zombi ezisinziira ku MRGPRB2 n’ezitali za MRGPRB2 okufulumya histamine, ekola hypothermia okuyita mu histamine H 1 receptors, nga selective antagonist pyrilamine oba ablation of H 1 receptors significantly attenuates this hypothermic effect.
Ebikolwa bya Melanotan-II
Omulimu mu kukola langi y’olususu
Ekimu ku bisinga okweyoleka mu MT-II kwe kuleeta langi y’olususu okweyongera, kwe kugamba, okutuuka ku kikolwa eky’okusiimuula. Ebiteeso okuva mu bakozesa biraga nti kumpi bonna abeetabye mu kutendekebwa kuno abaagezezzaako okutabula ne MT-II balaze okuddugala kw’olususu. Kino kiraga nti MT-II erina eddaala eritali limu ery’obwetwaze mu kuleeta langi y’olususu, nga teyesigamye mu bujjuvu ku busannyalazo bwa ultraviolet okutandika ebyuma ebikola melanogenesis.Mu kunoonyereza okumu, okwetegereza okuva mu bikolwa by’ebisolo n’okugezesa obutoffaali mu vitro kulaga nti MT-II esitula butereevu melanocytes, upregulating the expression of enzymes related to melanin synthesis, thereby promoting melanin and darkening langi y’olususu. Effect eno etuwa eky’okuddako eri abo abanoonya langi ya kikomo nga bwe beeraliikirivu olw’okwonooneka kw’olususu okuva mu UV.
Ebikosa Neurobehavior
Mu nsonga z’ebikolwa by’enneeyisa y’obusimu, MT-II eraga ebikolwa eby’enjawulo. Mu kunoonyereza nga bakozesa enseenene ng’ekyokulabirako, kyazuulibwa nti n’emmere ey’ekiseera ekitono erimu amasavu amangi (HF) (emala nga 1% yokka ku bulamu bw’ekyennyanja ky’empologoma, oba wiiki ssatu) esobola okuvaako okulemererwa okujjukira okutegeera, okweraliikirira okulinnya, n’okukendeeza ku mize gy’okunoonyereza mu byennyanja ebiyitibwa zebrafish. MT-II esobola okuzzaawo obutali bwa bulijjo buno obuleetebwa emmere erimu amasavu amangi, n’ezzaawo okujjukira kw’okutegeera kw’ensowera, okweraliikirira, n’enneeyisa y’okunoonyereza ku mitendera egy’enjawulo n’egyo egy’ekibinja ky’emmere eya bulijjo.
Mu kunoonyereza okwekuusa ku autism, nga bakozesa enkola y’ebibe ebiyamba obusimu obuziyiza endwadde (MIA) okukoppa autism, ebibe ebisajja ebya MIA biraga engeri eziringa autism, gamba ng’ebiraga enneeyisa y’abantu okukosebwa, okukendeeza ku mpuliziganya y’amaloboozi, n’okweyongera mu nneeyisa y’okuddiŋŋana. Oluvannyuma lw’ennaku musanvu ez’obujjanjabi bwa MT-II, ebiraga enneeyisa y’embeera z’abantu mu mbeba ensajja eza MIA byalongooka, ate ebiraga enneeyisa y’embeera z’abantu mu mbeba za C57 ezirina embeera eya bulijjo tebyalaga nkyukakyuka nnene oluvannyuma lw’okujjanjabwa MT-II. Kino kiraga nti MT-II erina ebiyinza okukolebwa mu bujjanjabi mu kulongoosa obuzibu mu nneeyisa eringa autism, okuwa endagiriro empya eri okunoonyereza ku bujjanjabi bwa autism.
Ekifaananyi 2 Ebibe ebisajja ebikulu ebya MIA byalaga okweyongera mu kwolesebwa kw’ekirungo kya oxytocin mu kitundu ky’omubiri ekiyitibwa anterior cingulate cortex.
Ebikosa enkyukakyuka y’amasoboza n’okutereeza ebbugumu
MT-II era erina kinene ky’ekola ku nkyukakyuka y’amasoboza n’okutereeza ebbugumu. Mu kugezesa kw’ebibe, ebibe ebirina obuzibu mu pituitary adenylate cyclase-activating peptide (PACAP) byaweebwa MT-II nga biyita mu mpiso ey’okumpi buli lunaku okumala wiiki ssatu ez’omuddiring’anwa mu kiseera ky’okutuukagana n’embeera ennyogovu. Ebivuddemu biraga nti MT-II esobola okuzzaawo ekitundu ku busobozi bw’okutonda ebbugumu obw’ebibe. Nga tupima norepinephrine-induced metabolic rate, kyazuulibwa nti obusobozi bwa thermogenic obw’ebibe ebyajjanjabwa ne MT-II bwakomezeddwawo ekitundu. Okugatta ku ekyo, obujjanjabi bwa MT-II bwatereeza obulema mu nkozesa y’amasavu wansi w’okusikirizibwa kwa adrenergic, ekiraga nti MT-II eyinza okukwata ku thermogenesis mu bitundu by’amasavu ebya kitaka nga etereeza emirimu gy’obusimu obw’okusaasira, bwe kityo n’ekola kinene mu kukuuma bbalansi y’enkyukakyuka y’amasoboza.
MT-II esobola okuleeta ebbugumu mu mbeba ng’ekola obutoffaali obuyitibwa mast cells n’okufulumya histamine. Enkola eno eraga omulimu gwa MT-II mu nkola z’okulungamya ebbugumu.
Ebiyinza okukosa enkola y’okuzaala
MT-II era erina ebiyinza okukosa enkola y’okuzaala. Kibadde kinoonyezebwa okujjanjaba obuzibu bw’okusituka, nga kino kyekuusa ku bikolwa byayo eby’okusitula enkola y’okuzaala.
Enkozesa ya Melanotan-II
Okukozesa mu mulimu gw’okwewunda
Mu by’okwewunda, MT-II esinga kukozesebwa ng’ekirungo ekirongoosa enviiri. Olw’okwagala okweyongera kw’olususu olulamu, olw’ekikomo n’okweraliikirira ku kwonooneka kw’olususu okuyinza okuva mu kukwatibwa omusana ogw’ekinnansi (nga okwokya omusana n’okwongera ku bulabe bwa kookolo w’olususu), MT-II efunye okufaayo ng’ekintu ekigambibwa nti kituuka ku kulongoosa nga tekyesigamye ku kukwatibwa musana. Wabula olw’okuba tennakkirizibwa bitongole birina buyinza nga FDA era nga terina kunoonyereza kwa maanyi ku by’okwerinda n’obulungi bwayo, okukozesebwa kwayo mu katale k’ebyokwewunda kukyali mu kifo enzirugavu. Mu nsi n’ebitundu ebimu, okutunda MT-II ku yintaneeti mu ngeri emenya amateeka olw’okwewunda oluusi n’oluusi kubaawo.
Okukozesebwa mu kunoonyereza ku by’obujjanjabi
Mu by’okunoonyereza ku by’obusawo, okukozesa MT-II okusinga essira erisinga kulissa ku kunoonyereza ku ngeri gy’eyinza okukozesebwa mu kujjanjaba endwadde ez’enjawulo. Mu mbeera y’obuzibu bw’enneeyisa y’obusimu, MT-II eraga obulungi mu kulongoosa obuzibu bw’enneeyisa y’obusimu obuleetebwa emmere erimu amasavu amangi mu zebrafish n’obutaba na nneeyisa eringa autism mu mbeba ensajja eza MIA, n’ewa endagiriro empya ez’okunoonyereza ku kujjanjaba obuzibu bw’obusimu obukwatagana.
Mu kunoonyereza ku nkyukakyuka y’amasoboza n’endwadde ezikwatagana n’okutereeza ebbugumu, MT-II’s salvage effect on thermogenesis in PACAP-deficient mice eraga omugaso gwayo oguyinza okubaawo mu kujjanjaba endwadde z’enkyukakyuka mu mubiri ng’omugejjo. Okwongera okunoonyereza ku nkola z’okulungamya eza MT-II ku makubo g’obubonero agakwata ku nkyukakyuka y’amasoboza kuyinza okuvaako okukola ebirungo ebipya ebijjanjaba obuzibu mu nkyukakyuka y’emmere. Okunoonyereza ku nkola ezisibukako MT-II-induced hypothermia era kuyinza okwongera okutegeera kwaffe ku nkola z’omubiri ez’okutereeza ebbugumu, okuwa omusingi gw’enzikiriziganya ogw’okujjanjaba endwadde ezikwatagana n’obutabeera bulungi mu kulungamya ebbugumu.
Mu nsonga z’endwadde z’enkola y’okuzaala, okunoonyereza ku nkozesa ya MT-II okujjanjaba obuzibu bw’okusituka, wadde nga kukyali mu mitendera gyayo egy’olubereberye, kuwa eky’okulonda ekipya eky’okujjanjaba obuzibu bw’okwegatta kw’abasajja.
Mu bufunzi
Melanotan-II, nga synthetic α-melanocyte-stimulating hormone analog, erina emirimu mingi egy’ebiramu egy’okukola langi y’olususu, enkola z’enneeyisa y’obusimu, okukyusakyusa amaanyi, okutereeza ebbugumu, n’enkola y’okuzaala. Mu nsonga y’okusiiga langi y’olususu, kiyinza okuleetera olususu okuddugala, ne kiwa ekkubo eriyinza okukolebwamu okuzimba. Mu kitundu ky’okunoonyereza ku by’obusawo, MT-II eraga essuubi erigazi ery’okukozesa. Okunoonyereza ku buzibu bw’enneeyisa y’obusimu, enkyukakyuka y’amaanyi n’endwadde ezikwatagana n’okutereeza ebbugumu, n’obuzibu bw’enkola y’okuzaala kuwa endagiriro empya ez’okujjanjaba embeera zino.
Ensonda
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[4] Gilhooley E, Daly S, McKenna D. Obumanyirivu bw’omukozesa wa Melanotan II: Okunoonyereza okw’omutindo ku bifo eby’okukubaganya ebirowoozo ku yintaneeti[J]. Ensusu, 2021, 237 (6): 995-999.DOI: 10.1159 / 000514492.
[5] Peters B, Hadimeri H, Wahlberg R, n’abalala. Melanotan II: ekiyinza okuvaako okuzimba ekibumba: okwekenneenya ebiwandiiko ne lipoota y’omusango[J]. Lipoota z’emisango gya Cen, 2020,9 (2): 159-161.DOI:10.1007/s13730-020-00447-z.
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Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
