Alpha 2 adrenoceptor potentiates glycine receptor-mediated taurine response
through protein kinase A in rat substantia nigra neurons.
Nabekura, Junichi, Tomohiro Omura and Norio Akaike.
Department of Physiology, Kyushu University, Faculty of Medicine, 3-1-1
Maidashi Higashi-ku Fukuoka, 812, Japan.
APStracts 3:0142N, 1996.
SUMMARY AND CONCLUSIONS
1. The modulatory effect of a2 adrenoceptor on the taurine response was
investigated in substantia nigra (SN) neurons acutely dissociated from the rat
using a nystatin perforated patch recording mode under voltage-clamp
conditions. 2. Complete cross-desensitization was observed between 10 -3 M
glycine and 3x10 -3 M taurine-induced currents. Both currents were antagonized
by 10 -6 M strychnine, thus indicating that taurine acts on strychnine-
sensitive glycine receptor on the SN neurons. 3. The simultaneous application
of norepinephrine (NE) with prazosin (10 -5 M) and propranolol (10 -5 M)
potentiated the taurine response (I tau ) in an NE concentration -dependent
manner at a holding potential (V H ) of -40 mV. Clonidine mimicked the NE
effect on the I tau , thus indicating the involvement of a2 adrenoceptor
activation in the potentiation of I tau . 4. Alpha 2 adrenoceptor activation
by NE with prazosin and propranolol significantly potentiated the peak
amplitude of I tau without shifting the taurine concentration-response
relationships either to left or right side. The respective concentrations of
taurine for the threshold, half maximal and maximal responses in the presence
of 10 -4 M NE with prazosin (10 -5 M) and propranolol (10 -5 M) were 3x10 -5
M, 3.1x10 -4 M and 3x10 -3 M. The same concentrations in the absence of NE
were 3x10 -5 M, 3.2x10 -4 M, and 3X10 -3 M, respectively. 5. The reversal
potentials of I tau with and without NE were very close to the theoretical Cl
- equilibrium potential, thus indicating that the potentiation of I tau by a2
adrenoceptor activation was due to an increase in the taurine-induced Cl -
currents. 6. Forskolin (3x10 -5 M) and isobutylmethylxanthine (IBMX, 3x10 -5
M) suppressed the peak amplitude of I tau . In the presence of dibutyryl
cyclic AMP (10 -4 M), which also suppressed I tau , a2 adrenoceptor activation
failed to potentiate I tau . 7. N-[2(methylamino)ethyl]-5-isoquinoline
sulfonamide dihydrochloride (H-89) mimicked the effect of a2 adrenoceptor
activation on I tau . In addition, the potentiation of I tau by a2
adrenoceptor was not observed in the presence of 10 -6 M H-89. 8. The
treatment of SN neurons with pertussis toxin (500ng/ml) for 18 hours
completely abolished the facilitatory effect of a2 adrenoceptor on I tau . 9.
These results suggest that the activation of a2 adrenoceptor coupled with IAP-
sensitive GTP binding protein decreases the intracellular cyclic AMP and
cyclic AMP-dependent protein kinase activity, thus resulting in the
potentiation of glycine receptor-mediated taurine response in rat SN neurons.
Received 5 February 1996; accepted in final form 11 June 1996.
APS Manuscript Number J93-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996