Influence of monensin on adriamycin transport and histamine release in rat peritoneal mast cells

Pharmacological

Research,

INFLUENCE

OF

Vol. 22, Supplement

MONENSIN

ON ADRIAMYCIN IN

E.

Crivellato, L.

Mallardi**, Institute

Human

and

Key

**

words:

One

Chair

the

resistance

cytotoxic

drugs, has

(1) which

hence

used

to It

bases,

normal

ionophore adriamycin

aim

OC with added

histamine

development

of

impair

MDR

recently

shown

and

peritoneal

cells

and

active

this

study

able

to

reverse

uptake

and

rat

peritoneal

was

that

was

to

1043-6618/90/2210133-02/$03.00/O

in

cells

adriamycin

exhibits

cells

by

by

organic

compartments, been

successfully

the in

for

cells

incubated

10

fluorimetric

other in

mast

resembles

to

a

carboxylic

also

able

to

mast

cells.

monensin, was

peritoneal

and

with

the

cells. if

rat

tremendous

adriamycin

closely

MDR

MDR

a

comparison of

which

monensin

the

in

evaluate

were

continued assayed

outside Many

acidic have

of

release

incubation

in

lysosomal

the

membrane.

accumulation

system

of

to

processes,

system

resistance

mast

alcaloids,

and

extruded plasma

mast

therefore

histamine

then

authors

vinca

endosomal

is

Recently

phoenomenon; and

gradients

that

transport

which

cells.

transport

concentrations

released

(2)

rat

outward

the

pH

lypophylic

mechanism.

MDR

the

with

the

the

the

are

of

accumulation,

anthracyclines

vescicles

in

of

and

of

Experimentally,

efflux

explain

and

resistance

an

various

pH,

traffic

neoplastic

Purified

University

range

alcaloids.

drug

in

membrane

mouse

dependent

The

F.

the

wide

drug

dependent

as

a

vinca

reduced

entrapped

containing

with

involves

energy

Candussioi,

Udine.

is

to

and

to

acidic

which

been

and

cells

was

an

drug

resistance

such

are

of

chemotherapy

a

drugs

have

reverse

for

L.

cells

anthracyclines

suggested

interfere

affinity

RELEASE

Pharmacology,

University

is

been

weak

has

that

energy

compounds,

and

HISTAMINE

Decorti*,

of

cancer

enhanced

these

cationic

in

an

that

Institute

mast

with

which of

as

proposed

vescicles,

AND

CELLS.

G.

Anatomy,

problems

has

are

fusion

Human

associated

hypothesis have

-L

monensin,

such

with

new

MAST

Klugmann”,

(MDR),

been

correlated a

of

major

multidrug

MDR

PERITONEAL

Anatomy,

adriamycin,

of

TRANSPORT

Baldini”.

of

Trieste

RAT

Bartoli

F.

133

I,1990

in

quadruplicate

than

adriamycin

additional

min. method

limit

at (50

The of

Shore

37

ug/ml)

amount et

o 1990 The Italian Pharmacological

of al.

Society

34

Pharmacological adriamycin

(3); Bachur

et

concentration

al.

(4).

epifluorescence a mercury A

vapor

10

dent

min

microscopy

using

of

cells with

before

prepared

cells.

were

exposed

a

maximal

nuclei

contrary,

in

fluorescence

was

fluorescent

periferal

hence

inhibits

adriamycin

evidence

is

transport of

C.N.R.

on

the

the

rat time

secreta-

of

monensin

effect.

cells

treated

intensely

with

fluorescent. only

cells

On

the

nuclear

large,

intensely

which

is

the

pleyotropic

known

release

of

disrupt

resistance

histamine about

to

phenotype,

in

the

similarities

MDR

cells,

endosomal

mast

cells.

Further

between and

also

the

the

energy

energy dependent

cells.

supported

Acknowledgements:

in

observed.

system

mast

depen-

release

Removal

mast

sporadic

monensin,

and

a dose

of

monensin,

in

with

inhibitory

in

with

equipped

dependent

min.

both

for

filter.

caused

the

that, were

were

inhibit

10

of

processed

barrier

addition

abolish

only

provided

outward

and

to uptake

mechanism

zione

that

therefore

not

K510

histamine

the

after

showed

present;

show

and

dependent

did

vacuoles

and

to

action

pretreated

still

a

was

prior

also

ug/ml)

uptake

cytoplasms

cells

results

influx

and

and

inhibition

monensin

were

I,1990

method

microscope

(0.6-150

of

examination

the

functions

degree

Vol. 22, Supplement

fluorimetric

above

filter

ug/ml)

adriamycin

the

Orthoplan

monensin

inhibitory by

detailed

excitation

to

by

Leitz

(50

The

microscopical

These

a

with

mast

adriamycin, the

BG12

measured as

adriamycin

stimulation

The

a

preincubation

peritoneal

gogue

Cells

lamp,

inhibition

that

was

Research,

by

Progetto

grants

from

Finalizzato

Minister0

Oncologia

della

Pubblica

contract

no

drug

resistance.

Istru-

88.00509.44.

References 1.

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in

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L, rat

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and isotopic