Protein phosphorylation in rat cerebral cortex after desipramine treatment

Pharmacological

Research

Communications,

Vol. 19, No.

961

12, 1987

PROTEIN PHOSPHORYLATION IN RAT CEREBRAL CORTEX AFTER DESIPRAMINE Perez

J.,

Center

Tinelli

of

D.,

Zanotti

Via Taramelli Desipramine,

protein

Considerable

evidences

indicate

biological

cyclic

the

of

of

analyze

rat

after

Sprague

Italy)

were

the

pattern

of

10 mg/kg received

were

killed

cortex

1 hour

(1983)

according

weight

treatment

last

slight

the

procedure

of

liquid The

cut

out

from

scintillation studies

phosphorylation incorporation kd in basal

herein

subjected

to

into

dried

presented

gels

and

frontal

cortex

of

River,

2 weeks;

bands

of

according

(1973).

cerebral to Ualaas

subjected

to SDS-PAGE The

gels

In

were

order

on different

P content

control

The animals

autoradiography. 32

Calco, DMI was

fractions

were

Favre

was

saline.

performed

protein

demonstrate

after chronic 32 of P in a protein conditions an endogenous

the

was

incorporation

and

study

gels,

to the

was quantitated

by

spectrometry.

represents assay

the

Laemmli

present

for of

Samples

adaptive

conditions.

Soluble were

modification.

destained, dried and 32 demonstrate the P incorporation were

injection.

that

of

Charles

daily

injection

assay

stained,

bands

of

phosphory-

antidepressant.

standard

twice

number

the

a tricyclic

in

intraperitoneally

the

gr,

modifying

the

number

in the

150-200

groups

phosphorylation

with

to

(body

thus

demonstrate

a

Aim of

(DMI),

),

for

with

many

concentration

(1983)

phosphorylation

desipramine

after

(Ca

al.

system.

protein

an equivalent

and protein

al.

by

et

produce

++

responsible

associated

monoaminergic

housed

and *Inst.

intracellular

or calcium

Racagni is

rats

Milan

neurotransmitters

enzymes

central

administered animals

kinases,

with

of

Italy.

the

GMP (cGMP)

the

Dawley

several

by regulating

proteins.

a treatment

Male

et

protein

of Pavia,

that

administration

in

to

Univ.

cyclic

substrate

antidepressant changes

9, Univ.

Balzaretti

phosphorylation.

responses

AMP (CAMP),

activity

lation

Via 14,

Key words:

of

G.

Neuropharmacology,

Pharmacology,

of their

W. and *Racagni

TREATMENT

performed

in

0031-6989/87/120961-02/$03.00/O

these

(Fig.

of

band of apparent In order

substrate

conditions

autoradiography

administration

1).

in

that

for

presence

DMI

of

demonstrates

shows

molecular

to demonstrate

the

of protein

CAMP. that 0 1987

The the

higher

weight

that

CAMP dependent

a

this

protein increase

of 280 protein kinase, 32 of P

280 kd protein

The Italian

Pharmacological

is Society

Pharmacological

962

Research

Communications,

Vol. 19, No.

12, 7987

3zP incorporation

Fig. 1: genous cortical

CAMP-dependent endophosphorylation of soluble fraction in

s~~"'p~c~~~o~~~i~~ea~~d

g,,

band (upper panel). Autoradiography of (6%) (lower panel).

effectively

phosphorylated

The high lation

molecular could

associated

acute

weight

suggest

protein

appears

to

in

biochemical

MAP-2.

the

of

phosphorylation

the

amount

substrate

the of

et

the

increased

modification the

protein;

catalitic c)

al.,

the

al.

this by

kinase

represent

the

of

induce

any

protein

can

Future

state

of kinase

or regulatory in

of

that

MAP-Z

Since

activity

intracellular

an

modification, be

the

related

to

with

tricyclic

these

studies

280 kd phosphorylation

subunits; the

microtubule

neurons.

treatment aim

kinase. phosphory-

demonstrated

portion

a chronic

1983).

protein

protein

(1984)

seem to

of protein

variation

may

dendritic

of induced

(Racagni whether

a)

the

et

DMI doesn't

modifications

investigate

protein

De Camilli in

CAMP dependent

CAMP dependent

this

be concentrated

antidepressants

due to:

and the

that

administration

change

by an endogenous

SDS-PAGE

or the b) the

is

to

can be variation

increase level

the

in of the

of

second

messengers. References: De Camilli, P., Miller, P.E., Navone, F., Theurkauf, W.E. and Vallee, (1984) Neuroscience 11, 819-846. Laemmli, U.K., and Favre, M. (1973) J. Mol. Biol., 80, 575-599. Racagni, G., Mocchetti, I., Calderini, G., Battistella, A. and Brunello, (1983) Neuropharmacology, 22, 415-424. Nairn, A.C., and Greengard, P. (1983) J. Neurosci, Walaas, S.I., 291-301.

R.B.

N. 3,