, , , -,

, ,

M

-

John Newport Langley (1852-1925) Paul Ehrlich (1854-1915)

/

/

(receptive)

(lateralchains, receptors)

-

H

-

. Ligand gated ion channel receptorsB. G-protein coupled receptors (GPCR). nzyme-linked receptors. Intracellular receptors

. - (Ligand gated ion channel receptors)

(cys-loop) 5 (2) . , GABAA, GABAC, , 5-HT3

4 . NMDA, AMPA,

( )

o . (ature, 2009)

- : (bungarotoxin): ( )

GABA

( )

GABAA

GABA

PKA

Y NMDA

NMDA ,

2 AMPA : Na+, +NMDA : Na+, Ca2+

-

- a+, Ca2+

5-HT3

- Cl-

GABA

( )

-

B. G- (G-protein coupled receptors, GPCRs)

1% , , , , ,

(1, 2, 2, 1, 2, 3) (D1, D2, D3) (m1-m5) (5-HT1, 5-HT2, 5-HT4 5-HT7)

7 (ransmembrane)

G-

(binding pocket) 3

GPCR

()

Asp 113 2 Asp 117 3

G

GPCR

(effector)

cAMP

( )

GPCR

(effector) C

IP3

DAG

GPCR

.. PKA (negative feed-back)

(Atropa belladonna) ( )

( )

.

2 :

.

..

.. D3

..

Hsp70Hsp70

HBD: Hormone Binding DomainNTD: Nuclear Translocation DomainHRE: Hormone Response Element

- (ligand gated ion channel receptors)

G (G-protein coupled receptors, GPCRs )

(enzyme-linked receptors)

(intracellular receptors)

/ -

- (voltage gated ion channels)

Na+ Ca2+ K+

-

-

a+, Ca2+

+

()

- (msec)- ( msec)

- +

Na+

S

10 nM: , .

1000 nM:

.

Na+

Na+

.

Na+

- Ca2+

4 (L, N, P, T). L (large):

- Ca2+

DHP: (.. )

PAA: (.. )

- K+

ICa

+ (transient outward K+ channels, Ito) 4--

+ (delayed rectifier K+ channels, Ikr) --

+ (inward rectifier K+ channels, Iki)

Ito Ikr

Iki

INa

/ -

-

. Na+/K+ ATP

.

.

. Na+/K+ ATP

a+ Ca2+

.

SSRIs (Prozac), TCA

,

(GABA) Gabatril

K -

.

. -

.

. P

V. ( )

()

14.000 /sec

. -

. -

A Physostigma venenosum Calabar Clermont

. -

M - - (, DPF) (, )

DPF

.

() (, , 5--)

(, Inhibitors of Monoaminoxidases)

- ( ) : ()

- () : (Parkinson, Alzheimer)

Mitogen-Activated Protein Kinases ()

. P

- in vitro

- /II

p38( )

p38 , , IL-1, TNF-a

15 48 p38

. P

V.

( Camptotheca accuminata) (Mandragora officinarum)

-

.

1. A : D

.. , ,

2. : D

.. , ,

3. : DNA RNA

..

1.A

()

G-C

2.

3.

(6-TG)

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