Na Cocer Peptides 
1 mahina aku nei
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a i ʻole maʻi. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.
Melanotan-II Overview
ʻO Melanotan-II (MT-II) kahi mea hoʻohālikelike α-melanocyte-stimulating hormone (α-MSH) no ka papa o ka melanocortin agonists. ʻAʻole hoʻohana wale ʻia ʻo MT-II no nā kumu pili i ka tanning; ma ke kahua o ka noiʻi olakino, ke ʻimi ʻia nei no nā noi kūpono i ka mālama ʻana i nā kūlana e like me ka erectile dysfunction.
Kiʻi 1 ʻO ke ʻano o Melanotan-II.
Melanotan-II Mechanism of Action
Hoʻohana mua ʻo MT-II i kāna mau hopena ma ka launa pū ʻana me nā melanocortin receptors (MCRs). ʻO ka ʻohana melanocortin receptor loaʻa nā subtypes he nui e like me MC1R, MC2R, MC3R, MC4R, a me MC5R. ʻO MT-II kahi agonist receptor melanocortin ʻole koho e hiki ke hoʻopaʻa a hoʻōla i nā MCR he nui.
I loko o ka ʻili, hoʻopaʻa ʻia ʻo MT-II i ka MC1R ma ka ʻili o nā melanocytes, e hoʻāla ana i ka adenylate cyclase, ka mea e hoʻonui ai i nā pae cyclic AMP (cAMP), a laila hoʻāla i ka protein kinase A (PKA). Hoʻoulu ka PKA i ka microphthalmia-associated transcription factor (MITF) ma o ka phosphorylation. ʻO MITF kahi kumu transcription koʻikoʻi i ka melanin synthesis, Hoʻoponopono ia i ka hōʻike ʻana o nā genes e like me tyrosinase, tyrosinase-related protein-1 (TRP-1), a me tyrosinase-related protein-2 (TRP-2), ʻo ia nā enzymes i komo i ka melanin synthesis, ka hopena e alakaʻi ai i ka hoʻonui ʻana i ka pigmentation ʻili a loaʻa kahi hopena tanning.
I loko o ka ʻōnaehana nūnū, hoʻopili ʻo MT-II i kekahi mau ʻōnaehana neuroendocrine. Hiki iā ia ke hoʻoulu i ka ʻōnaehana oxytocin waena. Ua hōʻike nā haʻawina i ka hoʻokomo ʻana i ka intravenous MT-II i ka hōʻike ʻana o Fos i nā neurons nui o ka suprachiasmatic nucleus (SON) a me ka paraventricular nucleus (PVN) o ka hypothalamus, kahi pane e hiki ke hoʻemi ʻia e ka intracerebroventricular injection mua o ka melanocortin antagonist SHU-9119. Hōʻike nā hoʻopaʻa leo electrophysiological i ka hoʻonui ʻia ʻana o ka intravenous injection o MT-II i ke kī ʻana o nā neurons oxytocin i ke SON akā ʻaʻole ia e hoʻokuʻu i ka dendritic oxytocin hoʻokuʻu i loko o ke SON. Ma muli o nā haʻawina mua e hōʻike ana i ka hoʻohana pololei ʻana o ka melanocortin agonists i ka supraoptic nucleus (SON) oxytocin neurons, hiki ke hoʻonui ʻia nā hopena o intravenous MT-II ma ka liʻiliʻi loa, ma o ka hoʻoulu ʻana i nā mea komo mai ka brainstem caudal, kahi e hoʻonui ai ʻo MT-II i ka ʻōlelo Fos.
Hoʻohui ʻia, loaʻa iā MT-II kekahi mau hana o ka hana i ka metabolism ikehu a me ka thermoregulation. I nā hoʻokolohua ʻiole, hoʻoulu ʻia ka intraperitoneal injection o MT-II i ka hypometabolism/hypothermia koʻikoʻi a transient. Nalo kēia ʻano hypothermic i nā ʻiole Kit W-sh/W-sh i nele i nā mast cell, e hōʻike ana he mea nui nā mast cell no MT-II-induced hypothermia. Hiki i ka MT-II ke hoʻoulu i nā mast cell ma o MRGPRB2-dependent a me -independent mechanisms e hoʻokuʻu i ka histamine, ka mea e hoʻopuka ai i ka hypothermia ma o ka histamine H 1 receptors, no ka mea, ʻo ka pyrilamine antagonist koho a i ʻole ka ablation o nā mea loaʻa H 1 e hoʻemi nui i kēia hopena hypothermic.
Nā hopena o Melanotan-II
Hana i ka ʻili ʻili
ʻO kekahi o nā hopena koʻikoʻi o MT-II ʻo ia ka hoʻoulu ʻana i ka hoʻonui ʻana i ka ʻili, ʻo ia hoʻi, ka loaʻa ʻana o ka hopena tanning. Hōʻike nā manaʻo mai nā mea hoʻohana kokoke i nā poʻe a pau i hoʻāʻo e hoʻomaʻamaʻa me MT-II i hōʻike i ka pōʻeleʻele o ka ʻili. Hōʻike kēia he ʻano kūʻokoʻa ko MT-II i ka hoʻoulu ʻana i ka pigmentation ʻili, ʻaʻole i hilinaʻi nui i ka radiation ultraviolet e hoʻomaka i ka mīkini melanogenesis. Hāʻawi kēia hopena i kahi koho ʻē aʻe no ka poʻe e ʻimi nei i ka ʻili keleawe me ka hopohopo e pili ana i ka pōʻino o ka ʻili i hoʻoiho ʻia e UV.
Nā hopena i ka Neurobehavior
Ma ke ʻano o nā hopena neurobehavioral, hōʻike ʻo MT-II i nā hana multifaceted. Ma nā haʻawina e hoʻohana ana i ka iʻa zebrafish ma ke ʻano he kumu hoʻohālike, ua ʻike ʻia ʻo nā meaʻai momona kiʻekiʻe (HF) no ka manawa pōkole (ʻo ka lōʻihi wale nō ma kahi o 1% o ke ola o ka iʻa zebra, a i ʻole ʻekolu pule) hiki ke alakaʻi i ka hoʻomanaʻo hoʻomanaʻo ʻana, piʻi aʻe ka hopohopo, a me ka hoʻohaʻahaʻa ʻana i ka ʻimi ʻimi i ka iʻa zebra. Hiki iā MT-II ke hoʻohuli i kēia mau mea ʻino i hoʻoulu ʻia e ka meaʻai momona nui, e hoʻihoʻi i ka hoʻomanaʻo ʻana o ka iʻa zebrafish, ka hopohopo, a me ka ʻimi ʻimi ʻana i nā pae e like me ka hui ʻai maʻamau.
Ma ka noiʻi e pili ana i ka autism, me ka hoʻohana ʻana i ka ʻiole maternal immune activation (MIA) e hoʻohālike i ka autism, hōʻike nā ʻiole kāne MIA i nā hiʻohiʻona like me ka autism, e like me nā hōʻailona o ka nohona pili kanaka, hoʻemi i ka kamaʻilio leo, a me ka hoʻonui ʻana i ka hana hou. Ma hope o ʻehiku mau lā o ka mālama ʻana i ka MT-II, ua hoʻomaikaʻi ʻia nā hōʻailona o ka nohona pili kanaka i nā ʻiole MIA kāne, ʻoiai nā hōʻailona o ka nohona pili kanaka i nā ʻiole C57 me kahi ʻano maʻamau i hōʻike ʻole i nā loli nui ma hope o ka mālama ʻana iā MT-II. Hōʻike kēia he hiki ke loaʻa i ka MT-II nā hopena therapeutic i ka hoʻomaikaʻi ʻana i nā hemahema ʻano like me ka autism, e hāʻawi ana i nā kuhikuhi hou no ka noiʻi lapaʻau autism.
Kiʻi 2 Ua hōʻike nā ʻiole MIA kāne makua i ka piʻi ʻana o ka hōʻike o ka oxytocin receptor i ka cortex cingulate anterior.
Nā hopena i ka ikehu metabolism a me ka thermoregulation
He hopena koʻikoʻi ko MT-II i ka metabolism ikehu a me ka thermoregulation. Ma nā hoʻokolohua ʻiole, ua lawelawe ʻia nā ʻiole me ka pituitary adenylate cyclase-activating peptide (PACAP) deficiency i MT-II ma o ka hoʻokele peripheral i kēlā me kēia lā no ʻekolu mau pule i ka wā hoʻololi anu. Ua hōʻike ʻia nā hopena e hiki i ka MT-II ke hoʻihoʻi hapa i ka mana thermogenesis impaired o nā ʻiole. Ma ke ana 'ana i ka norepinephrine-induced metabolic rate, ua 'ike 'ia ua ho'iho'i 'ia ka mana thermogenic o nā 'iole i mālama 'ia me MT-II. Hoʻohui hou, hoʻoponopono ʻo MT-II i nā hemahema i ka hoʻohana ʻana i ka lipid ma lalo o ka hoʻoulu ʻana adrenergic, e hōʻike ana e hiki i ka MT-II ke hoʻohuli i ka thermogenesis i loko o ka ʻiʻo adipose brown ma o ka hoʻoponopono ʻana i ka hana nerve sympathetic, no laila ke pāʻani nei i ke kuleana i ka mālama ʻana i ka pale metabolic ikehu.
Hiki i ka MT-II ke hoʻoulu i ka hypothermia i nā ʻiole ma ka hoʻoulu ʻana i nā mast cell a hoʻokuʻu i ka histamine. Hōʻike kēia kaʻina hana i ke kuleana o MT-II i nā mīkini hoʻoponopono wela.
Nā hopena hiki i ka ʻōnaehana hānau
Loaʻa i ka MT-II nā hopena kūpono i ka ʻōnaehana hānau. Ua aʻo ʻia no ka mālama ʻana i ka erectile dysfunction, e pili ana i kona hopena hoʻoulu i ka ʻōnaehana hānau.
Nā noi o Melanotan-II
Nā noi i ka ʻoihana nani
I ka ʻoihana nani, hoʻohana mua ʻia ʻo MT-II ma ke ʻano he mea hana tanning. Me ka ulu nui ʻana o ka ʻili keleawe a me nā hopohopo e pili ana i ka pōʻino o ka ʻili i hoʻokumu ʻia e ka lā maʻamau (e like me ka lā a me ka piʻi ʻana o ka maʻi maʻi ʻili), ua loaʻa ʻo MT-II i ka manaʻo ma ke ʻano he huahana i ʻōlelo ʻia e hoʻokō i ka tanning me ka hilinaʻi ʻole i ka ʻike ʻana o ka lā. Eia nō naʻe, no ka mea ʻaʻole i ʻae ʻia e nā ʻoihana mana e like me ka FDA a nele i ka nui o ka palekana a me nā haʻawina efficacy, ʻo kāna noi i ka mākeke nani e mau ana i kahi wahi hina. I kekahi mau ʻāina a me nā ʻāina, kūʻai ʻole ʻia ke kūʻai aku ma ka pūnaewele MT-II no nā kumu hoʻonaninani.
Nā noi ma ka noiʻi lapaʻau
Ma ke kahua o ka noiʻi olakino, ʻo ka noi ʻana o MT-II ka mea nui i ka ʻimi ʻana i kāna mau noi lapaʻau kūpono no nā maʻi like ʻole. Ma ka pōʻaiapili o nā maʻi neurobehavioral, ua hōʻike ʻo MT-II i ka maikaʻi i ka hoʻomaikaʻi ʻana i nā abnormalities neurobehavioral i hoʻoulu ʻia e ka momona momona i ka zebrafish a me ka autism-like behavioral deficits i nā ʻiole MIA kāne, e hāʻawi ana i nā kuhikuhi noiʻi hou no ka mālama ʻana i nā maʻi neurological pili.
Ma nā haʻawina o ka ikehu metabolism a me nā maʻi pili i ka thermoregulation, ʻo ka hopena hoʻopakele o MT-II i ka thermogenesis i nā ʻiole hemahema PACAP e hōʻike ana i kona waiwai kūpono i ka mālama ʻana i nā maʻi metabolic e like me ka momona. ʻO ka noiʻi hou aʻe i nā ʻōnaehana hoʻoponopono o MT-II ma nā ala hōʻailona pili i ka ikehu e hiki ke alakaʻi i ka hoʻomohala ʻana i nā mea lapaʻau hou no nā maʻi metabolic. ʻO nā haʻawina e pili ana i nā mīkini i lalo o MT-II-induced hypothermia hiki ke hoʻonui i ko mākou ʻike i nā kaʻina physiological o ka thermoregulation, e hāʻawi ana i kumu kumu no ka mālama ʻana i nā maʻi e pili ana i nā mea ʻino o ka thermoregulatory.
Ma ke kahua o ka reproductive system maʻi, noiʻi e pili ana i ka hoʻohana ʻana i ka MT-II no ka mālama ʻana i ka erectile dysfunction, ʻoiai aia nō i kāna mau pae mua, hāʻawi i kahi koho hou no ka mālama ʻana i ka male male.
Ka hopena
ʻO Melanotan-II, ma ke ʻano he synthetic α-melanocyte-stimulating hormone analog, loaʻa i nā hana biological e pili ana i ka pigmentation ʻili, nā kaʻina neurobehavioral, ka metabolism ikehu, thermoregulation, a me ka ʻōnaehana hānau. Ma ke ʻano o ka pigmentation ʻili, hiki iā ia ke hoʻoulu i ka pōʻeleʻele o ka ʻili, e hāʻawi ana i kahi ala kūpono no ka tanning. Ma ke kahua o ka noiʻi lapaʻau, hōʻike ʻo MT-II i nā manaʻo noiʻi ākea. ʻO ka noiʻi ʻana i nā maʻi neurobehavioral, ka metabolism ikehu a me nā maʻi pili i ka thermoregulation, a me nā maʻi ʻōnaehana reproductive e hāʻawi i nā kuhikuhi hou no ka mālama ʻana i kēia mau kūlana.
Nā kumu
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[2] Wekwejt P, Wojda U, Kiryk A. Melanotan-II hoʻohuli i ka hōʻino hoʻomanaʻo i hoʻoulu ʻia e kahi meaʻai HF pōkole [J]. Biomedicine & Pharmacotherapy, 2023,165:115129.DOI:10.1016/j.biopha.2023.115129.
[3] Tomassi S, Dimmito MP, Cai M, et al. CLIPSing Melanotan-II no ka ʻike ʻana i nā Agonists hMCR koho he nui [J]. Journal of Medicinal Chemistry, 2022,65(5):4007-4017.DOI:10.1021/acs.jmedchem.1c01848.
[4] Gilhooley E, Daly S, McKenna D. Melanotan II ʻIke Mea Hoʻohana: He Haʻawina Kūlike o nā Kūkākūkā Kūkākūkā Online[J]. Dermatology, 2021,237(6):995-999.DOI:10.1159/000514492.
[5] Peters B, Hadimeri H, Wahlberg R, et al. ʻO Melanotan II: kahi kumu kumu o ka infarction renal: loiloi o ka palapala a me ka hōʻike hihia [J]. Cen Case Reports, 2020,9(2):159-161.DOI:10.1007/s13730-020-00447-z.
[6] Paiva L, Sabatier N, Leng G, et al. Ka hopena o Melanotan-II ma ka Brain Fos Immunoreactivity a me ka Oxytocin Neuronal Activity and Secretion in Rats [J]. Journal of Neuroendocrinology, 2017,29(2).DOI:10.1111/jne.12454.
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