TY - JOUR
T1 - Effects of GABA on noradrenaline release and vasoconstriction induced by renal nerve stimulation in isolated perfused rat kidney
AU - Fujimura, Shinsei
AU - Shimakage, Hironori
AU - Tanioka, Hideki
AU - Yoshida, Makoto
AU - Suzuki-Kusaba, Mizue
AU - Hisa, Hiroaki
AU - Satoh, Susumu
PY - 1999
Y1 - 1999
N2 - 1. We examined effects of γ-aminobutyric acid (GABA) on vasoconstriction and noradrenaline (NA) release induced by electrical renal nerve stimulation (RNS) in the isolated pump-perfused rat kidney. 2. RNS (1 and 2 Hz for 2.5 min each, 0.5-ms duration, supramaximal voltage) increased renal perfusion pressure (PP) and renal NA efflux. GABA (3, 10 and 100 μM) attenuated the RNS-induced increases in PP by 10 -40% (P < 0.01) and NA efflux by 10-30% (P < 0.01). GABA did not affect exogenous NA (40 and 60 nM)-induced increases in PP. 3. The selective GABA(B) agonist baclofen (3, 10 and 100 μM) also attenuated the RNS-induced increases in PP and NA efflux, whereas the RNS-induced responses were relatively resistant to the selective GABA(A) agonist muscimol (3, 10 and 100 μM). 4. The selective GABA(B) antagonist 2-hydroxysaclofen (50 μM), but not the selective GABA(A) antagonist bicuculline (50 μM), abolished the inhibitory effects of GABA (10 μM) on the RNS-induced responses. 5. The selective α2-adrenoceptor antagonist rauwolscine (10 μM ) enhanced the RNS-induced responses. GABA (3, 10 and 100 μM) potently attenuated the RNS-induced increases in PP by 40-60% (P < 0.01) and NA efflux by 20-50% (P < 0.01) in the presence of rauwolscine. 6. Prazosin (10 and 30 nM) suppressed the RNS-induced increases in PP by about 70-80%. Neither rauwolscine (10 nM) nor GABA (10 μM) suppressed the residual prazosin-resistant PP response. 7. These results suggest that GABA suppresses sympathetic neurotransmitter release via presynaptic GABA(B) receptors, and thereby attenuates adrenergically induced vasoconstriction in the rat kidney.
AB - 1. We examined effects of γ-aminobutyric acid (GABA) on vasoconstriction and noradrenaline (NA) release induced by electrical renal nerve stimulation (RNS) in the isolated pump-perfused rat kidney. 2. RNS (1 and 2 Hz for 2.5 min each, 0.5-ms duration, supramaximal voltage) increased renal perfusion pressure (PP) and renal NA efflux. GABA (3, 10 and 100 μM) attenuated the RNS-induced increases in PP by 10 -40% (P < 0.01) and NA efflux by 10-30% (P < 0.01). GABA did not affect exogenous NA (40 and 60 nM)-induced increases in PP. 3. The selective GABA(B) agonist baclofen (3, 10 and 100 μM) also attenuated the RNS-induced increases in PP and NA efflux, whereas the RNS-induced responses were relatively resistant to the selective GABA(A) agonist muscimol (3, 10 and 100 μM). 4. The selective GABA(B) antagonist 2-hydroxysaclofen (50 μM), but not the selective GABA(A) antagonist bicuculline (50 μM), abolished the inhibitory effects of GABA (10 μM) on the RNS-induced responses. 5. The selective α2-adrenoceptor antagonist rauwolscine (10 μM ) enhanced the RNS-induced responses. GABA (3, 10 and 100 μM) potently attenuated the RNS-induced increases in PP by 40-60% (P < 0.01) and NA efflux by 20-50% (P < 0.01) in the presence of rauwolscine. 6. Prazosin (10 and 30 nM) suppressed the RNS-induced increases in PP by about 70-80%. Neither rauwolscine (10 nM) nor GABA (10 μM) suppressed the residual prazosin-resistant PP response. 7. These results suggest that GABA suppresses sympathetic neurotransmitter release via presynaptic GABA(B) receptors, and thereby attenuates adrenergically induced vasoconstriction in the rat kidney.
KW - GABA(B) receptor
KW - Noradrenaline release
KW - Rat kidney
KW - Sympathetic nerves
KW - γ-aminobutyric acid (GABA)
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U2 - 10.1038/sj.bjp.0702524
DO - 10.1038/sj.bjp.0702524
M3 - Article
C2 - 10369462
AN - SCOPUS:0032926585
VL - 127
SP - 109
EP - 114
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 1
ER -