Adenosine facilitates in vivo neurotransmission in the superior colliculus
of the rat.
HIRAI, Hirokazu, and Yasuhiro OKADA.
Department of Physiology, Kobe University School of Medicine, Kusunoki-cho,
7-5-1, Chuo-ku, Kobe 650, Japan. TEL 81-783417451 ex 3220, FAX 81-
783415732.
APStracts 2:0138N, 1995.
SUMMARY AND CONCLUSIONS
1. Electrical responses to volleys in afferent fibers in the optic tract were
recorded in the superficial gray layer of anesthetized rat superior
colliculus. A prominent negative wave with 4 - 6 ms peak latency in the upper
part of the superficial gray layer and a sharp negative wave with 1.5 - 2 ms
peak latency in the lower part of the superficial gray layer were elicited,
corresponding to the C2 (upper part of the superficial gray layer) and the C1
(lower part of the superficial gray layer) postsynaptic potentials reported by
Sefton. 2. These C1 and C2 waves were depressed by kynurenic acid or
quinoxaline dione (DNQX) applied just beside the recording electrode,
suggesting that neurotransmission in these pathways is mediated by glutamate.
3. Adenosine (10 [mu]M) injected in the superficial gray layer enhanced both
C1 and C2 potentials up to 170 and 140 %, respectively. 4. Administration of a
potent inhibitor of adenosine deaminase, erythro-9-(2-hydroxy-3-nonyl) adenine
hydrochloride (EHNA) (5 mg/kg, s.c.) increased the amplitudes of both C1 and
C2 potentials to 125 and 130 % of the initial levels, respectively.
5. The extracellular application of adenosine uptake inhibitors, dipyridamole
(100 [mu]M) and nitrobenzylthioinosine (NBI) (10 [mu]M) also enhanced
postsynaptic potentials. 6. Prior application of L -homocysteine thiolactone
(10 [mu]M), a compound which facilitates the incorporation of adenosine into
S-adenosylhomocystein, and reduces the extracellular concentration of
adenosine, attenuated the excitatory action of exogenously applied adenosine.
7. Excitatory effects were also observed upon application of a selective
adenosine A1 receptor agonist, N 6 -cyclohexyladenosine (CHA) or a selective
A2 receptor agonist, 2-[4-(2-carboxylethyl) phenethylamino]-5'N-
ethylcarboxamide adenosine hydrochloride, (CGS21680). Selective A1 and A2
receptor antagonists, 8-cyclopentyl-1, 3-dimethylxanthine (CPT) and 3,7-
dimethyl-1-propargylxanthine (DMPX), respectively, failed to suppress the
excitatory action by adenosine. However, combined application of these two
agents blocked the facilitatory action by adenosine on the excitatory
synapses. 8. The application of adenosine (10 [mu]M) to the superficial gray
layer via a microdialysis probe increased the glutamate release by about 230 %
of the basal level. Similarly, the administration of EHNA (5 mg / kg, s.c.)
enhanced the extracellular glutamate level up to about 170 %. However, prior-
application of L -homocysteine thiolactone (10 [mu]M) failed to potentiate the
glutamate release by adenosine. 9. This is the first in vivo study to
demonstrate an excitatory action of adenosine on synaptic transmission.
Present results clearly indicate that in the superficial gray layer of the rat
superior colliculus, extracellular adenosine has an facilitatory action on
neurotransmission generated by activation of retinotectal afferents and the
excitatory effect may be mediated by an increase in glutamate release. The
high activity of adenosine deaminase and intense localization of nucleoside
transporters in the superficial gray layer may contribute to the modulation of
the excitation caused by endogenously released adenosine or adenosine
hydrolyzed from released ATP.
Received 17 January 19954; accepted in final form 18 April 1995.
APS Manuscript Number J40-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.