Alpha-adrenergic regulation of the GABA-endogenous release in different rat cerebral cortex subregions

27

Pharmacological Research. Vol. 22. Supplement 3.1990

ALPHA-ADRENERGIC REGULATION OF THE GABA-ENDOGENOUS RELEASE IN DIFFERENT RAT CEREBRAL CORTEX SUBREGIONS A. Pittaluga, R. Torelli and M. Raiteri Istituto di

Farmacologia e Farmacognosia, Universita degli Studi

di

Genova, Viale Cembrano 4, 1614B Genova, Italy. Key words: GABA release, synaptosomes, cerebral cortex subregions It has been found that noradrenaline (NA) causes enhancement of

7f -aminobutyric

acid (GABA)

release in

rat hippocampus through the

activation of receptors which appear to belong to the 02 type (1-2). This work has now been extended to the study of the effect of the adrenergic agonist clonidine (CLO) on the basal release of endogenous GABA in superfused synaptosomes from whole rat cerebral cortex (3). CLO (0.001 - 1

~M)

caused a concentration-dependent increase of the

release of GABA. The effects of 0.1 to 1

CLO were only

~M

in part

sensitive to the 02 adrenoceptor antagonist yohimbine (YOI); a complete antagonism by YOI could be seen only with 0.001 the effect of 0.1 to 1 adrenoceptor

antagonist

~M

~M

CLO. On the contrary

CLO was increasingly sensitive to the 01

prazosin

(PRA). At all

the

concentrations

tested, CLO was fully antagonized by a mixture YOI-PRA (1 release

of

GABA

was

increased

concentration-dependent (0.01 - 1 antagonized by 1

~M

by ~M)

phenylephrine

manner. At 1

~M

(PHE)

~M).

in

The a

PHE was fully

PRA.

Studying the effect of

CLO

(0.005

~M)

or

PHE

(0.1

~M)

on

synaptosomes obtained from parietal, temporal and occipital cortex, the release of GABA was found to be region specific. CLO-induced GABA release could not be seen in temporal and occipital cortex but it was pronounced in parietal and frontal cortex. The effect

I 043-66 I 8j90j22IlI0027--o2jS03.00jO

©

1990 The Italian Pharmacological Society

28

Pharmacological Research, Vol. 22, Supplement 3,1990

of PHE did not parallel that of CLO: GABA release was most sensitive to PHE in the occipital cortex where CLO was ineffective. The opposite occurred in parietal

cortex synaptosomes,

where PHE was much

less

effective than CLO. In conclusion: 1)

CLO

stimulates

the

release

of

GABA

in

rat

cerebral

cortex

synaptosomes;

2) the

effect

is

likely

to

occur

by

activation

of

a

1

and

a

2

adrenoceptors possibly located on GABAergic nerve endings; 3) a differential distribution of a

and a adrenoceptors regulating 1 2 GABA release exists within the cortical subregions.

REFERENCES 1) Pittaluga A, Raiteri M. GABAergic nerve terminals in rat hippocampus possess a

2-adrenoceptors 1987; 76:363-367.

regulating GABA release.

Neurosci.

Lett.

2) Maura G, Pittaluga A, Ulivi M, Raiteri M. Enhancement of endogenous GABA release from rat synaptosomal

preparations

is

mediated, by

pharmacologically different from a ptors. 2-adrenoceptor 2-autorece Eur. J. Pharmacol. 1988; 157:23-29.

a

3) Raiteri M,

Bonanno G, Marchi M, Maura G. Is there a functional

1inkage between neurotransmitter uptake mechanisms and presynaptic receptors? J. Pharmacol. Exp. Ther. 1984; 231:671-677.