nikotin acetylcholine grahakam

nicotinic acetylcholine grahakaalu, ledhaa natures, neurotransmitter acetylcolineku pratispandinche grahaka polypeptides. nikotin grahakaalu agonist nikotin vanti aushadhaalaku kooda pratispandistaayi. avi kendra mariyu paridheeya naadii vyavastha, kandaraalu mariyu aneka itara jeevula kanajaalaalo kanipistaayi. kandaraala sankocham niyantrinche motaru naraala-kandaraala communication kosam kandaraalalo praathamika grahakam naadii kandaraala junction vadda untaayi. paridheeya naadii vyavasthaloh (1) avi saanubhootigala mariyu paracypathetic naadii vyavasthalooni postsinaptic kanaalaku presynaptic nundi avtgoing sankethaalanu prasaram chestaayi, mariyu (2) avi asthipanjara kandaraalapai kanipinche grahakaalu, ivi acetylcholine nuu sweekaristaayi, ivi kandaraala sankocham kosam sanketam. roganirodhaka vyavasthalo, natures ververu kanaantara maargaala dwara shotha prakriyalu mariyu sankethaalanu niyantristaayi. keetakaalalo, colinergic vyavastha kendra naadii vyavasthaku parimitam cheyabadindi.
nicotinic grahakaalu acetylcolineku pratispandistaayi kabatti vaatini colinergic grahakaalugaa pariganistaaru. nikotin graahakaalaku nikotin nundi vaari paeru vastundi, idhi mascarinic acetylcholine grahakalanu prerepinchadu, conny badulugaa nikotin graahakaalato empikagaa bandhistundi. mascarinic acetylcholine grahakam adevidhamgaa aaa graahakaaniki empikagaa jodinche rasaayanamaina muscarine nundi daani paerunu pondutundi. acetylcholine anedi mascarinic mariyu nicotinic acetylcholine graahakaalato bandhistundi.
ionotropic grahakaalagaa, naacharlu neerugaa ayan chaanellato anusandhaaninchabadi untaayi. eee grahakaalu konni sandarbhaallo rendava dhoothalu (jeevakriya graahakaala vale) kooda upayoginchavacchani kotta aadharalu suuchistunnaayi. nicotinic acetylcholine grahakaalu ionotropic grahakaalalo uttamamgaa adhyayanam cheyabadinavi.
nicotinic grahakaalu saanubhooti mariyu parasypthetic vyavasthalaku avtgoing sankethaalanu prasaram cheyadamlo sahaayapadataayi kabatti, hexamethonium vanti nicotinic grahaka satruvulu eee sankethaala prasaaramlo jokyam chesukuntaru. udaaharanaku, nikotin grahaka pratyarthulu baroreflexlo jokyam chesukuntaru, idhi saadhaaranamgaa gunde yokka saanubhooti mariyu paracypathetic uddeepana dwara raktapotulo maarpulanu sarichestundi.
nirmaanam.
290 kda paramaanu dravyaraasitoe nicotinic grahakaalu, aidu upabhaagaalato tayaaravutaayi, ivi kendra randhram chuttoo samaruupamgaa amarchabadi untaayi. prati upabhaagamlo naalugu transmembrane domainlu untaayi, enn-mariyu sii-terminus rendoo extracellularga untaayi. avi gaba grahakaalu, glycine grahakaalu mariyu rakam 3 serotonin grahakaalu (ivanni ionotropic grahakaalu) ledhaa signature sis-loop proteinlatho saaruupyatanu kaligi untaayi.
sakasherukaalalo, nikotin grahakaalu vaati praadhamika vyakteekarana pradaesaala aadhaaramgaa rendu upa rakaluga vistrutamgaa vargeekarinchabaddaayih "kandara-rakam" nikotin grahakaalu mariyu "neuronal-rakam" nikotin grahakaalu. kandaraala-rakam grahakaalalo, naadii kandaraala koodali vadda kanipinche, grahakaalu pinda roopam, 2:1:1:1 nishpattilo ((α1) 2β1γδ) loe α1, β1, γ, mariyu δ upaghatakaalato koodi untaayi, ledhaa 2:1:1:1 nishpattilo ((α1) 2β1δε) α1, β1, δ, mariyu ε upaghatakaalato koodi unna vayojana roopam. neuronal uparakaalu vividha homerick (anni oka rakamaina upaghatakam) ledhaa heteromeric (kaneesam oka α mariyu oka β) pannendu ververu nicotinic grahaka upaghatakaala kalayikalu α2 − α10 mariyu β2 − β4. neuronal uparakaala udaaharanalalo ivi unnaih (α4) 3 (β2) 2, (α4) 2 (β2) 3, (α3) 2 (β4) 3, α4α6β3 (β2) 2, (α7) 5, mariyu aneka itara. kandara-rakam mariyu neuronal-rakam grahakaalu rendintiloonuu, upabhaagaalu okadaanitoe okati chaalaa pooli untaayi, mukhyamgaa hydrophobic praantaalalo.
aneka electron microscopy mariyu ex-rae sphatika shaastra adhyayanalu kandaraalu mariyu neuronal naacharlu mariyu vaati binding domainla kosam chaalaa adhika spashtata gala nirmaana samacharanni andinchaayi.
bandham.
anni ligand-gated ayan chaanella maadirigaane, natcher chaanal randhram teravadaaniki rasayana sandesavaahakam yokka bandham avasaram. ligand, agonist ledhaa transmitter vanti grahakalanu bandhinche anuvulanu suuchimchadaaniki aneka vibhina padaalu upayoginchabadataayi. alaage antarjanyudaina agonist acetylcholine, natcher yokka agonists loe nikotin, epibatidine mariyu collin unnaayi. grahakanni nirodhinche nikotin vyatiraekulaloo mcamillamine, dihydro-beata-erythroidine mariyu hexamethonium unnaayi.
kandaraala-rakam naacharlalo, acetylcholine binding saitlu α mariyu ε ledhaa δ upa unitla interfacelo untaayi. neuronal naacharlalo, binding sait anedi α mariyu β subunit yokka interfaces vadda ledhaa α7 graahakaala vishayamlo rendu α subunitla madhya untundi. binding sait n terminus sameepamlo extracellular domainlo undhi. oka agonist saitku bandhinchinappudu, prastuta upabhaagaalannii conformational maarpuku lonavutaayi mariyu chhaanel teravabadutundi mariyu sumaru 0.65 nm vyaasamtho oka randhram teruchukuntundi.
chaanal teravadam.
nikotin assers vividha interconvertible conformational state laloe undavacchu. agonist yokka bandham bahiranga mariyu sunnitatvam laeni sthithulanu sthireekaristundi. saadhaarana saareeraka paristhitulalo, graahakaaniki teravadaaniki sarigga rendu anuvulu avasaram. chaanal teravadam valla sanukoolamgaa charge cheyabadina ayanlu daani gundaa kadaladaaniki veelu kalpistundi; mukhyamgaa, sodiyam kanamloki pravesistundi mariyu potassium nishkramanaku veelu kalpistundi. saanukuula charge ayanla nikara pravaham lopali vaipu untundi.
natcher anedi empika kaani katayan chhaanel, antey aneka vibhina saanukuula aavesam kaligina ayanlu daatagalavu. idhi Na + mariyu k + kuu paragamyam, konni upa-vibhagala kalayikalatho kooda ca2 + kii paragamyam. sodiyam mariyu potassium yokka parimaanam, chaanallu vaati randhraala dwara anumatistaayi (vaati vaahakata) 50 nundi 110 ps varaku maarutuu untundi, nirdishta upa-unit kuurpu mariyu paragamyam ayaannu batti vaahakata untundi.
aneka neuronal naacharlu itara neurotransmitterla vidudalanu prabhaavitam chestaayi. chhaanel saadhaaranamgaa vaegamgaa teruchukuntundi mariyu agonist vyaapti chendhe varaku terichi untundi, idhi saadhaaranamgaa 1 milliseconlu padutundi. hrs etuvanti ligandlatho kattubadi lekunda aakasmikamgaa teravavacchu ledhaa ligandlatho kattubadi aakasmikamgaa muusivaeyavachchu, mariyu chaanello utparivartanalu yea sanghatana yokka sambhaavyatanu marchagalavu. anduvalla, aach binding randhram teravadam yokka sambhaavyatanu maarustundi, idhi marinta aach bindsga perugutundi.
paamu visham α-neurotoxinlatho bandhinchabadinappudu natcher aachnu bandhinchaledu. eee α-neurotoxins asthipanjara kandaraala natures mariyu neuronlalo kathinamgaa mariyu samayojaneeyamgaa bandhistaayi, tadwara post synaptic pora vadda aach charyanu nirodhistaayi, ayan pravahanni nirodhistaayi mariyu pakshavaatam mariyu maranaaniki daariteestaayi. natcher loe paamu visham neurotoxinla kosam rendu binding saitlu unnaayi. eee pradaesaala bandhinche charya yokka gatiseelatanu kanugonadamlo purogati kashtamgaa niroopinchabadindi, ayinappatikee saadhaarana mode dynamicsnu upayoginche iteevali adhyayanalu paamu vishapadaardhaalu mariyu achh nundi natures yokka bandhinche vidhaanaala swabhaavaanni anchanaa veyadamlo sahayapaddayi. eee adhyayanalu aach binding valla kalige twist lanty kadalika randhram teravadaaniki kaaranamani, mariyu eee kadalikanu aapadaniki α-bangarotoxin (ledhaa itara podavaina golusu α-neurotoxin) yokka okati ledhaa rendu anuvulu saripothayani choopinchaayi. vishapadaardhaalu porugu grahaka upabhaagaalanu okadaanitoe okati mudipettinatlu anipistundi, idhi malupunu nirodhistundi mariyu anduvalla, prarambha kadalikanu nirodhistundi.
prabhavalu.
nikotin dwara graahakaala kriyaaseelata rendu pradhana vidhaanaala dwara neuronla sthithini savaristundi. oka vaipu, catayans kadalika plasma pora yokka vidhvamsamku kaaranamavutundi (idhi neuronlalo excitatory post synaptic potential kii daariteestundi) idhi voltage-gated ayan chhaanals yokka kriyaaseelataku daariteestundi. marovaipu, calcium pravesam, pratyakshamgaa ledhaa parokshamgaa, vividha kanaantara cascadelapy panichestundi. idhi, udaaharanaku, konni janyuvula karyakalapala niyantrana ledhaa neurotransmitterla vidudalaku daariteestundi.
niyantrana.
sunnitatvam tagginchadam.
graahakaala yokka ligand-bound desensitization modata nikotin acetylcholine graahakamlo cotz mariyu dusself dwara vargeekarinchabadindi.
oka uddeepanaku sudeerghamgaa ledhaa padepade bahirgatam kavadam valla tarachugaa aaa grahakam yokka pratispandana taggutundi, dheenini desensitization anie pilustaaru. rendava sandesavaahaka-aadhaarita protein kinesla kriyaaseelata dwara phosphorylation dwara natcher functionnu modulate cheyavachu. pica mariyu pikesi, alaage tyrosine kineslu, naachaarnu phosphorylate chestayani chuupabaddaayi, phalitamgaa daani desensitization jarugutundi. agonistku deerghakaala grahaka bahirgatam taruvaata, agonist swayamgaa graahakamlo agonist-prerita conformational maarpuku kaaranamavutundani nivedinchabadindi, phalitamgaa grahaka sunnitatvam taggutundi.
oka agonist saanukuula alosteric modulator samakshamlo kattubadi unnappudu desensitized grahakaalu sudeerghamaina bahiranga sthithiki tirigi raavacchu, udaaharanaku pᱱᱩ-120,596. eee grahakaalapai nirdishta chaperon anuvulu niyantrana prabhavalanu kaligi unnayani soochinche aadharalu kooda unnaayi.
paatralu.
nikotin graahakaala upabhaagaalu multigene kutumbaaniki chendinavi (maanavulalo 16 mandhi sabhyulu) mariyu upabhaagaala kalayikala yokka assembly pedda sankhyalo vividha graahakaalaku daariteestundi (marinta samacharam kosam ligand-gated ayan chaanal database chudandi). atyanta vaividhyamaina kinetic, electrophysiological mariyu pharmacological lakshanaalatoo kuudina eee grahakaalu nikotinku chaalaa bhinnamaina prabhaavavantamaina saandratalatoe bhinnamgaa pratispandistaayi. eee kriyaatmaka vaividhyam rendu pradhana rakaala neurotransmissionlo paalgonadaaniki veelu kalpistundi. shaastreeya synaptic transmission (wiring transmission) loe neurotransmitter yokka adhika saandratalu vidudala avtayi, idhi ventane porugu grahakaalapai panichestundi. dheeniki viruddhamgaa, paracrine transmission (valume transmission) loe oxon terminals dwara vidudala cheyabadina neurotransmitterlu untaayi, ivi adanapu-kana madhyamam dwara avi vaati grahakalanu cherukune varaku vyaapistaayi, ivi dhooramgaa undavacchu. nikotin grahakaalu vividha synaptic pradaesaalaloo kooda kanipistaayi; udaaharanaku kandaraala nikotin grahakam ellappuduu post-synapticga panichestundi. grahakam yokka neuronal roopaalu post-synapticalga (shaastreeya neurotransmissionlo palgontayi) mariyu prii-synapticalga rendintinee kanugonavacchu, ikkada avi bahula neurotransmitterla vidudalanu prabhaavitam cheyagalavu.
upabhaagaalu.
17 sakasheruka natcher upabhaagaalu gurtinchabaddaayi, ivi kandaraala rakam mariyu naraala rakam upabhagaluga vibhajinchabaddaayi. kodi vanti pakshula jaatulalo α8 upa-ekakam/janyuvu unnappatikee, idhi maanava ledhaa ksheerada jaatulalo undadu.
natcher upabhaagaalu protein kramamlo saaruupyata aadhaaramgaa 4 upa kutumbaluga (i-iv) vibhajinchabaddaayi. adanamgaa, upakutumbam III nuu 3 rakaluga vibhajinchaaru.
neuronal naacharlu anevi transmembrane proteins, ivi α2-α10 mariyu β2-β4 latho kuudina upa unitla kutumbam nundi sameekarinchabadina pentameric nirmaanaalanu yerparustaayi. eee upa unitlanu 1980la madhya nundi 1990la prarambham varaku kanugonnaru, eluka mariyu chiken medadula nundi bahula natcher upa unitla kosam cdnlanu clone chesinappudu, neuronal natcher upa unitla kosam padakondu ververu janyuvulanu (kollalo pannendu) gurtinchadaaniki daariteesindi; gurtinchina upa-unitla janyuvulaku α2-α10 (α8 kollalo matrame kanipistundi) mariyu β2-β4 anie paeru pettaru. vividha upa-unitla kalayikalu acetylcholine mariyu nikotin dwara sakriyam cheyagala kriyaatmaka naacharlanu roopondinchagalavani, mariyu vividha upa-unitla kalayikalu, vividha upa-aushadhaala yokka upa-rakalu mariyu kriyaatmaka lakshanaalatoo utpatti cheyagalavani kooda kanugonabadindi. ontarigaa vyakteekarinchinappudu, α7, α8, α9, mariyu α10 kriyaatmaka grahakalanu yerparustaayi, conny itara α upaghatakaalaku kriyaatmaka grahakalanu roopondinchadaaniki β upaghatakaala uniki avasaram. ksheeradaalalo, natcher upaghatakaalu 17 janyuvula dwara encode cheyabadinatlu kanugonabaddayi, veetilo, tommidi janyuvulu α-upaghatakaalu mariyu moodu encoding β-upaghatakaalu medadulo vyakteekarinchabadataayi. β2 upa-unitlatho kuudina natures (β2nachr) mariyu mariyu medadulo vistrutamgaa vyakteekarinchabadataayi, ayithe itara natcher upa-unitlaku marinta parimita vyakteekarana untundi. natures yokka pentameric assembly maanava oopiritittulalo vividha kana rakaalalo utpatti ayye upabhaagaalaku lobadi untundi, ikkada epithelial mariyu kandaraala pentamerlu ekkuvagaa bhinnamgaa untaayi.
chrna5/a3/b4.
oka mukhyamaina natcher janyu samuuhamloo (chrna5/a3/b4) α5, α3 mariyu β4 upaghatakaala janyuvula sanketeekarana untundi. janyu adhyayanalu eee moodu natcher janyuvulanu encoding chese chromosome lokaslo single nucleotide polymorphisms (snps) nuu nikotin aadharapadatam, oopiritittula cancer, deerghakaalika obstructive pulmonary vyaadhi, madyapaanam mariyu paridheeya dhamani vyaadhiki pramaada karakaluga gurtinchaayi. Chrna5/a3/b4 natcher subunit janyuvulu chromosome praantam 15q 24-25 loe oka bigutu samuuhamloo kanipistaayi. eee locus dwara encode cheyabadina natcher subunitlu paridheeya naadii vyavastha (pns) loe vyakteekarinchabadina pradhana nikotin grahaka uparakaalanu mariyu itara keelaka kendra naadii vyavastha (cns) saitlanu yerparustaayi, madhya naadii vyavastha (cns) vanti limbic forbrain mariyu madhya medadu madhya nirmaanam pradhana colinergic circuit margalalo paalgontundi. chrna5/a3/b4 janyuvula yokka tadupari parisoedhana "neuronal" natcher janyuvulu kooda neuronal kaani kanaalalo vyakteekarinchabadataayani, avi vaapu vanti vividha praathamika prakriyalalo paalgontaayani velladinchindi. chrna5/a3/b4 janyuvulu aneka kana rakaalalo saha-vyakteekarana cheyabadataayi mariyu moodu janyuvula prothsaahaka praantaala yokka transcription karyakalapalu oke transcription kaarakaala dwara niyantrinchabadataayi, vaati clustering janyu vyakteekarana yokka niyantrananu pratibimbistumdani niroopistundi.
chrna6/chrnb3.
chrnb3 mariyu chrna6 kooda kooda unna janyu samuuhamloo samuuhaparachabaddaayi. samuuhaparachabaddaayi snaps nikotin aadharapadatam mariyu dhumapana pravartanatho mudipadi unnayani bahula adhyayanalu choopinchaayi, chrnb3, rs6474413 mariyu mariyu rendu snaps vantivi. eee praantamloo janyu vaividhyam kokain mariyu madyam viniyogamtho sahaa durviniyoga mandulanu upayoginchadaanni kooda prabhaavitam chestundi. medadu praantaalalo, mukhyamgaa ventral tegmental praantam mariyu substantia nigraalo vyakteekarinchabadina α6 ledhaa β3 upabhaagaalanu kaligi unna nicotinic grahakaalu, dopamine vidudalalo vaati paatra kaaranamgaa aushadha pravartanalaku mukhyamainavi. eee janyuvulalo janyu vaividhyam, protein yokka amaino aamlam nirmaanaanni marchadam ledhaa transcriptional mariyu translational regulationlo maarpulaku kaaranamavadam vanti aneka vidhaluga durviniyoga mandula patla sunnitatvaanni maarchagaladu.
chrna4/chrnb2.
baga adhyayanam cheyabadina itara natcher janyuvulalo chrna4 mariyu chrnb2 unnaayi, ivi autosomal dominant noctornal frontal lobe muurcha (adnafel) janyuvulugaa sambandham kaligi unnaayi. eee rendu natcher upabhaagaalu medadulo untaayi mariyu eee rendu upabhagalalo utparivartanalu sambhavinchadam anedi muurcha yokka saadhaarana rakaniki kaaranamavutundi. udaaharanalalo ratriputa muurchalu mariyu manasika rugmatalato sambandham unna chrna4 insersion mutation 776in3, mariyu muurchaku matrame kakunda, abhyasam mariyu ghnaapakasakti lopaalu vanti chaalaa nirdishta abhignaa lopaalanu kooda kaliginche chrnb2 mutation i312m unnaayi. eee rendu janyuvula madhya sahajamgaa sambhavinche janyu vaividhyam mariyu single nucleotide polymorphisms (snp) mariyu itara janyu maarpula vislaeshanha chrnb2 janyuvu kante chrna4 janyuvulo adhika vaividhyaanni chooputundi, idhi chrnb2 dwara encode cheyabadina protein ayina natchr natchr, α4 kante ekkuva subunitlatho anubandham kaligi undani suuchistumdi. chrna2 kooda ratriputa frontal lobe muurchalaku moodava abhyardhigaa nivedinchabadindi.
chrna7.
aneka adhyayanalu manasika rugmatalu mariyu nikotin aadharapadatam yokka chrna7 mariyu endophenotypla madhya anubandhaanni nivedinchaayi, idhi α7 yokka gananeeyamaina clinical auchityaaniki dohadam chestundi mariyu daanipai parisoedhanalu jarugutunnaayi. schizophreniatho sambandham kaligi unnatlu pariganinchabadina modati janyuvulalo chrna7 okati. schizophreniatho sambandham unna janyuvula transcriptional karyakalapalanu tagginche aneka chrna7 promotor polymorphismlanu adhyayanalu gurtinchaayi, idhi schizophrenic rogula medadulo a7 natures yokka taggina sthaayilanu kanugonadamtho sthiramgaa untundi. schizophrenia unna vyaktula postmartem adhyayanaalalo natures uparakaalu, α4β2 mariyu α7 rendoo gananeeyamgaa tagginatlu kanugonabadindi. adanamgaa, schizophrenia unnavaarilo dhumapanam raetlu gananeeyamgaa ekkuvagaa untaayi, idhi nikotin dhumapanam anedi sweeya-vaidyam yokka oka roopam kaavacchu anie suuchistumdi.
gurtinchadagina vaividhyaalu.
nicotinic grahakaalu eee upabhaagaala pentamerlu; i.ii.prati graahakamlo aidu upabhaagaalu untaayi. anduvalla, eee upa unitla yokka vaividhyam yokka apaaramaina sambhaavyata undhi, veetilo konni itarulakanna saadhaaranamgaa kanipistaayi. atyanta vistrutamgaa vyakteekarinchabadina uparakaalalo (α1) 2β1δε (vayojana kandaraala rakam), (α3) 2 (β4) 3 (ganglian rakam), (α4) 2 (β2) 3 (cns-rakam) mariyu (α7) 5 (maroka cns-rakam) unnaayi. oka poolika krindi vidhamgaa untundih

