Opposite modulatory effects of substance P on GABA-and 5-HT-activated currents in the same sensory neurons.
The modulation by substance P of gamma-aminobutyric acid (GABA)- and 5-hydroxytryptamine (5-HT)-activated currents (I(GABA) and I(5-HT)) was studied by using patch-clamp technique in rat trigeminal ganglion (TG) neurons. The majority of neurons examined responded to GABA and 5-HT with inward currents in the same cells (63.8%, 30/47). In 22 out of 30 neurons sensitive to both GABA and 5-HT, pretreatment with substance P (SP, 0.01 micromol/L) suppressed I(GABA) by (35.7 +/-6.1)% and enhanced I(5-HT) by (65.2 +/- 8.7)%. GR 82334, a potent and specific antagonist of NK1 tachykinin receptor, reversibly blocked the modulatory effects of SP. The SP modulation on I(GABA) and I(5-HT) was also abolished by intracellular dialysis of GDP-beta-S, a non-hydrolyzable GDP analog, or GF 109203X, a selective protein kinase C inhibitor. These results suggest that SP exerts opposite modulatory actions on GABA(A) receptor and 5-HT3 receptor activity of the same primary sensory neuron via the same intracellular signal transduction pathway.
Hu
Wang-Ping
WP
Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Li
Zhi-Wang
ZW
Ru
Li-Qiang
LQ
Fan
You-Zhen
YZ
D000818:Animals; D000831:Animals, Newborn; D018756:GABA Antagonists / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D013373:Substance P; D005680:gamma-Aminobutyric Acid