D, Day giaocam Co tron mCilchth~n
1 Phenethanolamin N-methyl transferase HO
HO H~CH2-CH-NH2 tOOH 1 L- aromatic amino acid decarboxylase Tyrosin 3,4- dihydroxy phenylalanin (DOPA) HO ~~ Dopamin HO~CH2-CH2-NH2 1 Dopamin-p-hydroxylase Norepinephrin (noradrenalin) ---
1 Phenethanolamin-N- methyl transferaseHO HO
HO=:O-CH2-CH2-NH-CH3
6H
Epinephrin (adrenalin)
se do 4.1.cac giai doan sinh t6ng hopeateeholamin
1.3.2. Sinh t{j'ng hflp va chuye"n luia acetylcholin (hinh 4.3)
Sinh to"ng hflp
Sinh tang hop acetylcholin (Ach) a h~ pho giao cam duoc thuc hien bang each acetyl hoa cholin vdi acetyl coenzym A (CoA), dudi s,! xiic tac cua cholinacetyltranferase (ChAT). Acetylcholin duoc tich luy trong cac hat nho a ngon day than kinh dudi dang phuc hop khong co hoat tinh. Dudi anh huang cua xung d{>ngthan kinh, acetylcholin duoc giai phong se tac dung len cac receptor cholinergic (cholinoceptor).
:o-~I • :O-anxI-II. :o-~I
rn l\W) ~ I rn l\W) ~ I rn
Adrenalin Acid 3,4-dihydroxy Noradrenalin
(Epinephrin) mandelic (Norepinephrin)
terM terM terM
:o-~I ;:C-anxI-I• I.. ;:o-~I
rn l\W) ~ I rn l\W) ~ I rn
Metanephrin Acid 3-methoxy-4-hydroxy
mandelic (VMA)
Scsdo4.2. Chuy~n hoa catecholamin trong co th~
Normetanephrin
Chuyln hoa
Acetylcholin bi mat hoat tinh rat nhanh dudi tac dung cua cholinesterase (AchE) d~ tao thanh cholin (tiep tuc tham gia tang hop acetylcholin) va acetat.
1.4. Cite h~ phan ung cua h~ thlln kinh thuc v~t
1.4.1. H~ cholinergic
H~ thong cac thu th~ co ph an ling d~c hieu vdi acetylcholin goi la h~ phan ling vdi acetylcholin hay h~ cholinergic (cholinoceptor). H~ nay chu yeu co d mang sau synap hach giao cam, hach pho giao cam, mang sau synap sci sau hach pho giao cam va mang sau synap than kinh- co. Chung duoc chia thanh 2 h~ nho la he muscarinic (he M) va h~ nicotinic (he N).Ngoai ra, cdch~ nay con thay d than kinh trung uong.
1.4.1.1. H~ muscarinic
H~ muscarinic la h~ ngoai phan ling vdi acetylcholin con bi kich thich boi muscarin va hi phong be bdi atropin. Trong cd th~, h~ nay co d mang sau synap sqi sau h:;tchpho giao cam va tuyen m6 hoi.
Hi~n nay, ngudi ta tim ra 5 lo:;tireceptor cua h~ muscarinic: MI, M2, M3,
M4, M5.Receptor MI, M3, M5co d cd.trdn khi phe quan, tieu hoa, tiet ni~u, h:;tch va tuyen tiet. Receptor M2 va M4 co nhieu d cd tim va Cdtrdn m:;tchmau.
Khi kich thich h~ muscarinic gay co cd trdn khi phe quan, tieu hoa, tiet ni~u, U'mgtiet dich, gian cd trdn m:;tchmau, lie che tim va h:;thuyet ap.
1.4.1.2. H¢ nicotinic
H~ nicotinic la h~ ngoai phan ling vdi acetylcholin con hi kich thich bdi nicotin d lieu thap va hi phong he' hdi nicotin d lieu cao. H~ nicotinic co d cac hach giao cam, hach pho giao cam, han van dong cd xuong va tuyen tuy thuong than.
Khi kich thich h~ nicotinic gay co co van, kich thich tim, co mach, tang huyet ap, gian dong tti.
1.4.2. H~ adrenergic
H~ thong cac thu th~ co chung d~c tinh ph an ling dac hieu vdi adrenalin hoac noradrenalin duoc goi la he phan ling vdi adrenalin hay h~ adrenergic (adrenoceptor).
H~ adrenergic co chu ye'u d
mang sau synap sei sau hach giao cam. Cfing duoc chia thanh 2 h~ nho
la h~ u- adrenergic va h~ ~- adrenergic. CHOLINERGIC I Hemicholinium ~Y>/ ~ 1ft ~'Cholin Acetyl-CoA + Cholin tlChATI Ach )-- Vesamicol Botulinum ~=:::::::::~ Ch+olin Ach ""'it V ~ IAChE I Acetat 1.4.2.1. H¢ a- adrenergic
H~ c- adrenergic hao g6m cac
receptor U1 va u2. Hinh 4.3. SinhtOnghop,dl!trir,giaiph6ng
vaehuy~nh6aellaaeetyleholin
Receptor U1 co d mang sau
synap sci sau hach giao cam,
tren co tron mach mau ngoai vi, dudi da, n(>itang, co vong tieu hoa, tie't ni~u, cd tia mong miit. Khi kich thich receptor u1 gay co cd trdn ml:;lchmau va tang huye't ap, co cd tia mong milt lam gian d6ng tti, co cd trdn tie't ni~u. - Receptor U2 n&md mang truoc synap cua sqi sau hl:;lchgiao cam di toi cd
trdn ml:;lchmau, ti~u cl1u,te' hao rna. Khi kich thich receptor U2 lam giam tie't renin, gian ml:;lchva hl:;lhuye't ap, tang ke't dinh ti~u cl1u.
6 ngoq,i vi, receptor al chie'm ztu the' nen khi kich thich h¢ a- adrenergic ngoq,i vi thztiJng gay comq,ch va tang huye't ap.
1.4.2.2. H¢ f3- adrenergic
H~ ~- adrenergic co 3 lOl:;lireceptor la ~l' ~2 va ~3·
Receptor ~l co d mang sau synap cua sqi sau hl:;lchgiao cam chi phoi hOl:;lt d(>ngcua tim.
Receptor ~2 co d mang sau synap cua sci sau hach giao cam d co tron mach mau, phe' quan, tieu hoa, tiet nieu, co van, h~ chuyen hoa glucid.
Receptor~3 co d cac mo rna.
Khi kich thich h~ ~ gay kich thich tim, tang co bop co tim, gian cac co tron, tang chuyen hoa,
1.4.3. H~ dopaminergic
H~ nay co nhieu d co tron mach mau than, n9i tang va d than kinh trung uong, co 51o~i receptor nhung quan trong nhat la receptor D. va D2• Trong do, d ngoai vi receptor D. chiern uu the hon D2, nguoc lai, d trung uong D2 lai chiem uu the hon D1•Receptor D. co chu yeu d co tron mach than. Vi vay, khi kich thich h~ dopaminergic ngoai vi gay gian co tron mach than.
1.5.Co che phan tit khi kich thich h~ adrenergic va cholinergic
(hinh 4.4 va 4.5)
Khi co kich thich, xung d9ng than kinh se duoc d~n truyen theo chieu thuan, doc theo neuron tign h~ch Wi cac c4c t~n cling lam va cac bqc nho, giai phong cac chat hoa hqc, cac chat nay se vUQtqua khe synap va g~n vao h~ phan ling d mang sau synap (cholinoceptor ho~c adrenoceptor) lam thay d6i tinh tham cua mang te bao vdi cac ion Na+,K+,Cart, Cr. .. gay bien cl;ic(uu cl;icho~c khi't Cl;iC)lam d~n truygn tiep xung d9ng thlln kinh d day sau h~ch va gay ra dap ling sinh hqc tren co quan dich.
Tac d\lng cua cac catecholamin tren h~ adrenergic va acetylcholin tren h~ cholinergic dUQcthl;iChi~n thong qua cac receptor n&mtren mang te bao. Cac receptor nay c~p doi vdi protein G (guanyl nucleotid). Co khoang 20 lo~i protein G, trong do quan trqng nhat la 31o~i:
Gi: la protein G lic che adenylcyclase. Gs: la protein G kich thich adenylcyclase. Gp: protein G kich thich phospholipase C.
Mc3iprotein G dgu dUQccau t~o bdi 3 ti~u don vi la a, ~va y.
Khi chat d~n truygn hoa hqc g~n vao cac th\l th~ thi phlic hQp giua chat trung gian hoa hQc-th\l th~ se n6i vdi protein G (Gs, Gi ho~c Gp) gay cam ling ho~t hoa ho~c lic che adenylcyclase, phospholipase C, AMPv phosphodiesterase va cac kenh ion... lam anh hUdng tdi vi~c dong md cac kenh Cart, K+,Na+ gay tac d\lng sinh hqc.
Hinh 4.4. Sinh tong hop, chuy~n h6a va giai ph6ng cac catecholamin
1.5.1. H~ adrenergic (xem them bang 4.1)
1.5.1.1. Receptor a,
Receptor 0.1c~p doi vdi protein Gp. Khi cac catecholamin gAn vao receptor
0.1tren mang te' bao, lam hoat h6a receptor nay gay kich thich protein Gp. Khi d6 cac ti~u don vi a cua protein Gp tach ra, de'n hoat h6a phospholipase Clam tang thuy phan polyphosphoinositid tao thanh inositoltriphosphat (IP3) va diacylglycerol (DAG). IP3 co vai tro kich thich giai phong Ca'" tl! do tu noi du
tru, lam tang nong dQ Ca'" trong bao tuong, d6ng thoi hoat hoa protein kinase phu thuoc Ca++,lam md kenh Ca'", tang n6ng dQ Ca'" nQi bao gay nen co co tron mach mau, tang huyet ap va co co tron tie't nieu ... (hinh 4.5.D)
1.5.1.2. Receptor a2
Khac vdi tren receptor 0.1' receptor 0.2nam d mang trudc synap va cap doi vdi protein Gi nen khi kich thich receptor 0.2- adrenergic lam uc che' adenylcyclase, giam giai phong catecholamin gay uc che rim, gian mach, ha huye't ap va tang ke't dinh ti~u c~u (hinh 4.5. A, B, C).
1.5.1.3. Receptor fJ
Receptor ~- adrenergic (cii ~l' ~2va ~3) dgu cap doi vdi protein Gs. Khi cac catecholamin g&n vao receptor ~- adrenergic se hoat h6a adenylcyclase qua protein Gs, lam tang AMPv, gay kich thich tim, gian co tron va tang chuyen h6a (hinh 4.5.A).
A
Tebao dfch
D
c
Hinh 4.5. Co chetac dl:mg cua h~ than kinh thucv~t
A. Receptor Pl' P2'U2cap d6i vCliprotein Gs.B. M¢t56te bao, receptor U2 cap d6i vCliprotein G.