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.
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