Enhancement of GABA-activated currents by arginine vasopressin in rat dorsal root ganglion neurons / 生理学报

A growing number of studies have shown that arginine vasopressin (AVP) plays an analgesia role in the modulation of nociception. Previous studies have focused on the central mechanisms of AVP analgesia. The aim of the present study was to find out whether peripheral mechanisms are also involved. The effect of AVP on GABA-activated currents (IGABA) and GABAA receptor function in freshly isolated dorsal root ganglion (DRG) neurons of rats were studied using whole cell patch clamp technique. The result showed that, IGABA were potentiated by pre-treatment with AVP (1 × 10⁻¹⁰-1 × 10⁻⁵ mol/L) in a concentration-dependent manner. Meanwhile, the GABA concentration-response curve was shifted upwards, with an increase of (49.1 ± 4.0)% in the maximal current response but with no significant change in the EC50 values. These results indicate that the enhancing effect is non-competitive. In addition, the effects of AVP on IGABA might be voltage-independent. This potentiation of IGABA induced by AVP was almost completely blocked by the V1a receptor antagonist SR49059 (3 × 10⁻⁶ mol/L). Also it could be removed by intracellular dialysis of either GDP-β-S (5 × 10⁻⁴mol/L), a non-hydrolyzable GDP analog, or GF109203X (2 × 10⁻⁶ mol/L), a selective protein kinase C (PKC) inhibitor, with the re-patch clamp. These results suggest that AVP up-regulates the function of the GABAA receptor via G protein-coupled receptors and PKC-dependent signal pathways in rat DRG neurons, and this potentiation may underlie the analgesia induced by AVP.

Interaction of 5-HT2 and 5-HT3 receptor subtype in 5-HT-induced nociceptive responses in peripheral primary sensory nerve ending / 中国应用生理学杂志

<p><b>AIM</b>To study the correlation between 5-HT-induced pain response and the contribution by individual 5-HTR subtypes including 5-HT1R, 5-HT2R and 5-HT3R at the level of peripheral primary afferent.</p><p><b>METHODS</b>The experiments were done on acutely isolated trigeminal ganglion (TG) neurons using whole-cell patch clamp technique and the nociceptive effect was observed on behavior experiments by intraplantar injection of test drugs.</p><p><b>RESULTS</b>The majority of cells examined responded to 5-HT in a manner of concentration dependence (10(-6) - 10(-3) mol/) (61.4%, 54/88) and with a fast activating and rapid desensitizing inward current (I(5-HT)), which was thought to be mediated by the activation of 5-HT3R, since it could be blocked by 5-HT3R antagonist ICS 205930 and mimicked by 5-HT3R agonist 2-methyl-5-HT. It was found that I(5-HT) was potentiated by 5-HT2R agonist alpha-methyl-5-HT markedly, while 5-HT1R agonist R-(+)-UH 301 did not. In behavioral experiment performed on conscious rats, intraplantar injection of 5-HT(10(-5), 10(-4) and 10(-3) mol/L) induced an increment of cumulative lifting time first 20 min in a manner of concentration dependence. By dissociating 5-HTR subtypes using their corresponding antagonists (ICS and CYP) the potency order of hindpaw lifting time was identified as follows: 5-HT > 5-HT + ICS > 5-HT + CYP.</p><p><b>CONCLUSION</b>The results suggest that in 5-HT-induced nociceptive response at the primary sensory level 5-HT3R may play a role of initiation, but 5-HT2R mediates maintaining and modulatory effect in the processes of nociceptive information convey.</p>

Opposite modulatory effects of substance P on GABA-and 5-HT-activated currents in the same sensory neurons / 生理学报

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.

Study of effect and mechanism of midbrain periaqueductal gray NO on development of hypertension in stressed rats / 中国应用生理学杂志

<p><b>AIM</b>To study the role of NO in the midbrain periaqueductal gray (PAG) in the development of stress-induced hypertension (SIH).</p><p><b>METHODS</b>The model of stress-induced hypertension (SIH) rat was established by electric-foot in company with noise, NADPH-d histochemistry technique was used to investigate the change of nitric oxide synthase (NOS) positive neurons. Selecting and using microinjection and radioimmunoassay, we studied the effects of blood pressure and the content of Ach in rostral ventrolateral medulla (RVLM) after microinjection of L-NNA into PAG.</p><p><b>RESULTS</b>(1) The blood pressure increased, the cell number decreased and the grey degree value increased for the NOS positive neurons of PAG dorsolateral subdivision in SIH rats, and the content of Ach increased in RVLM. (2) Following microinjection of 100 mmol/L 0.1 microl L-NNA into PAG, the mean arterial pressure (MAP) and the content of Ach in RVLM increased in control rats, whereas the change of MAP was significantly smaller in SIH rats than control.</p><p><b>CONCLUSION</b>The plastic change of NOS positive neurons of PAG in SIH rats may be involved in the development of SIH, which may be mediated by Ach in RVLM.</p>