[Inhibition by SKF38393 of GABA-activated currents in rat DRG neurons].
Experiments were performed on neurons freshly isolated from rat DRG using whole-cell patch-clamp techniques. The majority of the neurons examined were sensitive to GABA (60/70) in the concentration range from 10(-6) to 10(-3) mol/L, showing obvious desensitization. In the 60 GABA-sensitive cells, responses induced by selective agonist of dopamine D1 receptor SKF38393 [(+/-) SKF38393HCL] manifested three types: (1) outward current (7/60); (2) inward current (5/60) and (3) no detectable response (48/60). As compared with GABA-activated current, the amplitude of SKF38393-activated current are smaller and showed no apparent desensitization. When the neurons were treated with SKF38393 prior to application of GABA for 30 s, the GABA-activated current in majority of the cells (53/60) was inhibited, while the remaining six showed no effect. The effect of SKF38393 was dose dependent. That is, with SKF38393 at concentration of 10(-7), 10(-6), 10(-5) and 10(-4) mol/L, the GABA-activated current was inhibited by (24.8 +/- 2.6)% (n = 7), (26.8 +/- 1.5)% (n = 7), (35.6 +/- 1.2)% (n = 8) and (45.6 +/- 2.3)% (n = 8) respectively. By intracellular application of 10(-4) mol/L H-7, a potent inhibitor of protein kinase, the inhibitory effect of SKF38393 was abolished completely, a results suggesting that the inhibition by SKF38393 of the GABA-activated current might be a result of intracellular phosphorylation of GABAA receptor.
Li
Q
Q
Research Centre of Experimental Medicine, Tongji Medical University, Wuhan 430030.
Wang
Q W
QW
Li
Z W
ZW
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D017447:Receptors, Dopamine D1; D005680:gamma-Aminobutyric Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine