Cerebrovascular and cerebrometabolic effects of intracarotid infused platelet-activating factor in rats

PROSTAGLANDINS

CEREBRO”*SC”LAR

AND

CEREsROHET*BOLIC

PLATELET-ACTIVATING J.A.. and

Evans

FACTOR

R.W.,

Padiatrlcs,

and

Burke

blood

brain flow

TO

Of

clearance) groups

of

pmOl,mi". to

77

+

6

contr*st, (p

<

for

1

mm

and

CBF

0.05).

affects

hypapcrfuslon

9.3

(p

=

of

PAF

reperfusion and

NS

+

12 +

and

to

116

0.9

rendered

into

the

1.6

and

9.6

+

the normal

pathoge"eStS

of

cerebral

+

14

from

122

mL,1GOg,mln to

was

143

(p

11.5

+

22

mL/100g/mln

in

at

2

artery +

(

1.4 by

+

(hydrogen

measured carotid

hypotensive

CBF 2.1

CSF

were

pressure

SimiLarly

vehicle,

in on

right

mL/IOOg/min

PAF

Medicine

USA.

metabolism, (CMROP)

arterial

the

for on

+

9.7

(n.7) with

CHROZ

raspectrva1y

159

from

controLs infused

and

The

from

mean

effects

oxygen

infused

decreased

increased

In and

porti?chemls

septic

Hg

CMROZ

h

Care

described. CBF

for

Hexadecyl-PAF

its

been

alters

rate

Helick

PennsyLvania.

implicated

but

not

PAF

metaboLic

rats.

n-10)

mL/lOOg/min h

c~r.sCraL

have that

E.M.,

*nesthcPio,ogy,Crit,cal

has'bcen shock

fNF”SED

Nemoto

Pittsburgh,

(PAF)

metabolism

INTR*C*ROTID

P.H.,

Of

Pittsburgh,

endotoxic

hypothesis

wistar

withdrawa,

1

and

the and

and

OF

Kocnanek Depts

factor

injury

(CBF)

test

EFFECTS

RATS

O.F.

""lversity

Platelet-activating I*chemlc

IN

4

(X

(70 +

SEW)

0.002).

In

ml/lOOg/min blood

and

137

baseline

)

21

and

after

both). CIF

and

hypermetabolism

and

CHROZ

endotoxin seen

mimic

those

infusion. in

the

PAF brain

observed may after

during

contribute ischemia

to and

the during

shock.

H. DOLY, P. BRAQUET,M. MILLKNIN,A. lXIF.FSW, J. CLUKSL and G. NEYNIEL BiophysicLab. INSEW U.71 and IHB Res. Labs. 63 Clermont-Ferrand and Le Plessis-Robinson (France). Platelet-activating factor (PAF)is a patent autacoidmediator inplicatedin a diverse range of human pathologies,includingoculardisease.It has been recentlyreported (Bussolinoet al. J. Biol. Chem. 1986,261, 16592)that PAF is secretedby vertebrateretinawhen stimulatedby various neurotransmitters. Using [ HI-PAFwe have been able to demonstratethe presenceof specificbinding sites for the mediator in the mannalienretina. In our experimentswe investigatedthe binding of the labelledautacoid in rat dark-adaptedretinas and total membraneextract.The binding characteristicsof the specificsites identifiedwere Kd = 2.9 i 0.4 nN ; Saxax= 0.85 + 0.16 pnol/mg psotein. The PAF-antagonists, gitigolideB (BN 52021) and NF.B2086 were able to totally displace [ HI-PAF from the specificretinalbindingsites. In order to determinethe inplications of PAF binding to the retina with regard to visual we examined the functionalactivity of rat isolated retina by measurementof the p?XXSS*SS, electroretinogram(91. Trea-lft of the retina with PAF decreasedthe ERG amplitude in a doseM), and this affect was totally inhibitedby concomitantad&dependentmanner (lo- M -> 10 nistrationof PAP antagonists. These resultsmay be interpretedin terms of the nwlecularevents involvedin the visual process. Retinal excitationcorrespondsto activationof transducin,which is a specificvariety of G-protein.Initialexperimentsindicatethat both PAF and BN 52021 may act directlyon transducin. Thus the effects of PAF on the retinamay be related to its abilityto inactivatetransducin,a process which is inhibitedby PAF-antagonists.

830

MAY 1988 VOL. 35 NO. 5