Biomedical subjects

I Yoshiya

Publications and source records attributed to I Yoshiya.

At least 19 recordsLinked to original sources

PubMed2001

Generation of hepatitis C virus-specific cytotoxic T lymphocytes from healthy individuals with peptide-pulsed dendritic cells.

BACKGROUND AND AIMS: In hepatitis C virus (HCV) infection, cytotoxic T lymphocytes (CTL) are involved in liver inflammation and contribute to the reduction of viral load. Antibodies for HCV-CTL precursor frequencies (CTLpf) are relatively low in chronic hepatitis C, and this may be related to the poor CTL response in vivo. The aim of this study was to assess the efficacy of dendritic cells (DC) as antigen-presenting cells in CTL generation from low CTLpf. METHODS: To confirm the rationale of using DC to prime naive T cells, five HCV-uninfected individuals were enrolled in the study. We obtained DC by maturation from peripheral progenitors under stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and IL-1alpha. Autologous T cells were cultured with DC or concanavalin-A-induced blasts loaded with four HCV-derived peptides bearing human leukocyte antigen (HLA)-A*0201 or -A24 motifs for 28 days under IL-7 and IL-2 stimulation. The lytic activity against peptide-pulsed targets was assessed by using a [51Cr]-releasing assay. RESULTS: The DC strongly expressed HLA class I, II, B7-1 and B7-2, but not phenotypic markers of T-, B-, natural killer (NK)-cells or monocytes. The CD8-positive, HLA-class I-restricted and HCV peptide-specific CTL were generated with DC from HLA-A antigen-matched subjects, whereas no CTL activity was detected with concavalin (Con-A) blasts. We were thus able to generate HCV specific CTL from naive precursors with peptide-pulsed DC. CONCLUSIONS: This DC-based system can be used to generate CTL of desired antigen specificity, even from a source with low CTLpf.

Adult↗

PubMed2001

Practical issues in bispectral analysis of electroencephalographic signals.

IMPLICATIONS: The aim of this report was to confirm the methodology of bispectral analysis of electroencephalogram. In developing a software for real-time bispectral analysis, we encountered several practical problems in bispectrum calculation. We settled those and concluded that 3 min of monitoring are required to obtain reliable and reproducible bicoherence values.

Algorithms↗

PubMed2001

Glucocorticoid suppresses neutrophil activation in ventilator-induced lung injury.

OBJECTIVE: To investigate, in a rat model, the role of the Mac-1/ICAM-1 pathway and the anti-inflammatory activity of steroid in ventilator-induced lung injury. DESIGN: Prospective, randomized controlled study. SETTING: Animal investigation using Wistar rats. INTERVENTION: Rats in three randomly assigned groups of 18, a total of 54 animals, were subject to the following: Two groups received high peak inspiratory pressure (35 cm H2O) ventilation after pretreatment with methylprednisolone (high-methylprednisolone group) or pretreatment with methylprednisolone vehicle (high-vehicle group). The third group of animals received low peak inspiratory pressure (7 cm H2O) ventilation after pretreatment with methylprednisolone vehicle (low-vehicle group). Except for animals previously killed to establish baseline values, after 40 mins of mechanical ventilation, the animals in each group were killed. Some animals provided histological samples, and the rest received total lung lavage. MEASUREMENT: We measured flow cytometry of lavage fluid, cell counts of tissue samples, and pressure-volume curves before and after mechanical ventilation. RESULTS: In the groups that received high peak inspiratory pressure ventilation, both the number of neutrophils that infiltrated the lungs and the expression of Mac-1 and ICAM-1 on neutrophils and macrophages increased significantly more than in the low-vehicle group. Static lung compliance was reduced in the high peak inspiratory pressure groups. In the high peak inspiratory pressure groups, there were significantly fewer neutrophils in samples from the high-methylprednisolone group (0.412 +/- 0.1 x 10(5)) than from the high-vehicle group (1.10 +/- 0.1 x 10(5); p < .05). The high-vehicle group showed greater expression of CD11b on neutrophils, but this was significantly decreased by methylprednisolone (mean fluorescence intensity: high-vehicle, 118.4 +/- 34.3; high-methylprednisolone, 25.8 +/- 4.2; p < .05). The lung mechanics measured by pressure-volume curve analysis were deteriorated less in the high-methylprednisolone group. CONCLUSION: Our study suggests that a neutrophil-endothelium interaction via the Mac-1/ICAM-1 pathway is involved in the activation and recruitment of neutrophils in ventilator-induced lung injury. Activation and recruitment of neutrophils were lessened by pretreatment with methylprednisolone, which might have contributed to the improvement of lung dysfunction after mechanical ventilation.

Animals↗

PubMed2000

The alpha and gamma subunit-dependent effects of local anesthetics on recombinant GABA(A) receptors.

Although convulsions due to local anesthetic systemic toxicity are thought to be due to inhibition of GABA(A) receptor-linked currents in the central nervous system, the mechanism of action remains unclear. We therefore examined the effects of local anesthetics on gamma-aminobutyric acid (GABA)-induced currents using recombinant GABA(A) receptors with specific combinations of subunits. Murine GABA(A) receptors were expressed by injection of cRNAs encoding each subunit into Xenopus oocytes. The effects of local anesthetics (lidocaine, bupivacaine, procaine and tetracaine) on GABA-induced currents of receptors expressing different subunit combinations (alpha1beta2, alpha1beta2gamma2s, alpha4beta2gamma2s and beta2) were examined via the two electrode voltage clamp method. At alpha1beta2, alpha1beta2gamma2s and alpha4beta2gamma2s GABA(A) receptors, all local anesthetics inhibited GABA-induced currents in a dose-dependent manner. The presence of the gamma2s subunit resulted in a greater inhibition by all local anesthetics, but the presence of the alpha4 subunit resulted in less inhibition. At beta2 homomeric receptors, local anesthetics directly induced an outward current similar to that of picrotoxin. These data indicated that (1) the alpha and gamma subunits of GABA(A) receptors modulated the inhibitory effects of local anesthetics on GABA(A) function, and (2) local anesthetics can activate the beta2 subunit and may block the GABA(A) receptor channel pore.

Anesthetics, Local↗

PubMed2000

Treatment of acute right coronary artery occlusion during anesthesia.

PURPOSE: Perioperative coronary artery occlusion is a potentially dangerous complication causing myocardial infarction and circulatory collapse. We report a case showing severe ST segment depression in leads II and V5 during anesthesia. Diltiazem and nifedipine, but not nitroglycerine, partially improved the ST changes which were normalized by a percutaneous cardiopulmonary system (PCPS). CLINICAL FEATURES: A 71-yr-old man with cerebrovascular disease was scheduled for coronary artery bypass grafting (CABG). Past medical history included myocardial infarction due to right coronary artery (RCA) occlusion. Both the femoral artery and vein were cannulated percutaneously before operation and the PCPS was prepared as a back-up system. Depression of the ST segments in leads V5 and II was observed following heparinization. Although hemodynamic stability was maintained with continuous infusion of catecholamines, the ST changes were not improved by intravenous nitroglycerine. Intravenous diltiazem followed by nasal nifedipine partially improved the ST changes. The changes were normalized after induction of PCPS. No neurological complications were observed. The postoperative coronary angiography confirmed the total occlusion of RCA. CONCLUSION: Calcium channel blockers were more effective than nitroglycerine in treating perioperative ST depression. However, none of them produced complete reversal of the ischemic changes which were normalized with PCPS.

Acute Disease↗

PubMed2000

Direct inhibition of microtubule-based kinesin motility by local anesthetics.

Local anesthetics are known to inhibit neuronal fast anterograde axoplasmic transport (FAAT) in a reversible and dose-dependent manner, but the precise mechanism has not been determined. FAAT is powered by kinesin superfamily proteins, which transport membranous organelles, vesicles, or protein complexes along microtubules. We investigated the direct effect of local anesthetics on kinesin, using both in vitro motility and single-molecule motility assays. In the modified in vitro motility assay, local anesthetics immediately and reversibly stopped the kinesin-based microtubule movement in an all-or-none fashion without lowering kinesin ATPase activity. QX-314, a permanently charged derivative of lidocaine, exerted an effect similar to that of lidocaine, suggesting that the effect of anesthetics is due to the charged form of the anesthetics. In the single-molecule motility assay, the local anesthetic tetracaine inhibited the motility of individual kinesin molecules in a dose-dependent manner. The concentrations of the anesthetics that inhibited the motility of kinesin correlated well with those blocking FAAT. We conclude that the charged form of local anesthetics directly and reversibly inhibits kinesin motility in a dose-dependent manner, and it is the major cause of the inhibition of FAAT by local anesthetics.

Adenosine Triphosphatases↗

PubMed2000

Intrathecal lithium reduces neuropathic pain responses in a rat model of peripheral neuropathy.

We tested the ability of lithium (Li(+)) to block heat hyperalgesia, cold allodynia, mechanical allodynia and mechanical hyperalgesia in rats experimentally subjected to painful peripheral neuropathy. Chronic constrictive injury (CCI) to the sciatic nerve induced persistent hyperalgesia and allodynia. Intrathecal injection of Li(+) (2.5-40 micromol) into the region of lumbar enlargement dose-dependently reduced heat hyperalgesia, cold allodynia and mechanical allodynia for 2-6 h after injection, but had no effect on mechanical hyperalgesia. Li(+) had no significant effect on responses from control and sham-operated animals. Intrathecal injection of myo-inositol (2.5 mg) significantly reversed both the anti-hyperalgesic and anti-allodynic effect of Li(+). These findings suggest that intrathecal Li(+) suppresses neuropathic pain response in CCI rats through the intracellular phosphatidylinositol (PI) second messenger system in spinal cord neurons. Lithium (Li(+)) has already found widespread clinical application; these results suggest that its therapeutic utility may be extended to include treatment of neuropathic pain syndromes resulting from peripheral nerve injury.

Animals↗

PubMed2000

Infrared transmission of electronic information via LAN in the operating room.

Recent advances in technology have brought many kinds of monitoring devices into the operating room (OR). The information gathered by monitors can be channeled to the operating ward information system via a local area network (LAN). Connecting patients to monitors and monitors to the LAN, however, requires a large number of cables. This wiring is generally inconvenient and particularly troublesome if the layout of the OR is rearranged. From this point of view, wireless transmission seems ideally suited to clinical settings. Currently, two modes of wireless connectivity are available: radio-frequency (RF) waves or infrared (IR) waves. Some reports suggest that RF transmission is likely to cause electromagnetic interference (EMI) in medical devices such as cardiac pacemakers or infusion pumps. The risk of malfunctioning life-sustaining devices and the catastrophic consequences this would have on seriously ill patients rules out the use of RF. Here, we report an IR system using IR modems for LAN connectivity in the OR. In this study, we focused on the possible detrimental effects of EMI during wireless connectivity. In our trial, we found no evidence of EMI of IR modems with any of the medical devices we tested. Furthermore, IR modems showed similar performance to a wired system even in an electrically noisy environment. We conclude that IR wireless connectivity can be safely and effectively used in ORs.

Hospital Information Systems↗

PubMed2000

Pulmonary disposition of propofol in surgical patients.

BACKGROUND: The lungs have been mentioned as a possible site contributing to the extrahepatic clearance of propofol. The objective of the present study was to clarify the pulmonary disposition of propofol directly in human lungs by investigating both the first-pass uptake and pulmonary extraction at pseudo-steady state. METHODS: Nine patients were enrolled in the first-pass uptake study. Propofol (5 mg) and indocyanine green (ICG; 15 mg) were simultaneously administered via a central venous catheter within 1 s, and sequential arterial blood samples were obtained from the radial artery at 1-s intervals up to 45 s. Eleven patients were included in the infusion study, and propofol was infused via the jugular vein at a rate of 50 microgram. kg-1. min-1. Blood samples were simultaneously collected from pulmonary and radial arteries up to 60 min. RESULTS: A pronounced difference in the dilution curves between propofol and ICG was observed, and 28.4 +/- 11.6% (mean +/- SD) of propofol was taken up during the single passage through the human lung. The mean pulmonary transit time of propofol (31.3 +/- 6.0 s) was significantly longer than that of ICG (22.4 +/- 2.7 s; P < 0.01), indicating that some of the propofol trapped by lungs returned to the circulation by back diffusion. In the constant infusion study, no significant differences were observed with the plasma concentrations of propofol between pulmonary and radial arteries except for that at 2 min. The area under the curve of pulmonary and radial arterial concentration curves to 60 min were 59.1 +/- 14.8 and 56.8 +/- 12.5 microg. ml-1. min-1, respectively. No significant difference was observed with the area under the curve, suggesting that metabolism was not involved in the pulmonary uptake in human lungs. CONCLUSIONS: Most of the propofol that undergoes pulmonary uptake during the first pass was released back to the circulation by back diffusion. Metabolism was not involved in the pulmonary uptake in human lungs.

Anesthesia, General↗

PubMed2000

Optimal level of pressure support ventilation for recovery from diaphragmatic fatigue in rabbits.

OBJECTIVE: To determine whether there is an optimal level of pressure support ventilation (PSV) for recovery from acute diaphragmatic fatigue. DESIGN: Prospective laboratory trial. SETTING: Experimental laboratory. SUBJECTS: Twenty healthy adult New Zealand White rabbits. INTERVENTIONS: Diaphragmatic fatigue was induced with 50 Hz of phrenic nerve stimulation for 30 mins. Recovery was compared between inspiratory load + PSV of 0 cm H2O (L0), inspiratory load + PSV of 60 cm H2O (L60), inspiratory load + PSV of 80 cm H2O (L80), and PSV of 0 cm H2O without inspiratory load (SB) for 90 mins immediately after the end of the fatigue-inducing procedure. To add inspiratory load during the recovery phase, three pressure threshold valves, each having an opening pressure of -20 cm H2O, were used. MEASUREMENTS AND MAIN RESULTS: After the fatigue-inducing procedure, diaphragmatic electromyogram and transdiaphragmatic pressure remained at baseline in both SB and L60, decreased in L80, and increased in L0. Recovery was assessed by abdominal cavity pressure (Pabd) generated by high-frequency (100 Hz) and low-frequency (20 Hz) stimulation. Pabd at 100 Hz recovered to baseline in L60 and SB but not in L0 and L80 (69.1%, 81.3%, 100.3%, and 100.7% of the baseline at 90 mins for L0, L80, L60, and SB, respectively). Pabd at 20 Hz did not differ among ventilatory settings. CONCLUSION: There is an optimal range of PSV assist level to improve recovery from diaphragmatic fatigue. Recovery was hampered not only by inadequate PSV but also by excessive PSV.

Airway Resistance↗

PubMed2000

[Comparison of propofol and isoflurane anesthesia on postoperative nausea, vomiting and pruritus induced by epidural morphine].

We compared propofol-nitrous oxide anesthesia (Group P) with isoflurane-nitrous oxide anesthesia (Group I) on the incidence of postoperative nausea, vomiting and pruritus induced by epidural morphine. Twenty-eight patients for thoracotomy for lung surgeries were randomly assigned either to Group P or Group I. All patients were administrated epidural morphine (4-7 mg.day-1) during and after the operation. The incidence of nausea, vomiting and pruritus was evaluated at the postoperative early (< 9 hour) and late (> 9 hour) periods. In the late postoperative period, in Group P the incidence of nausea and vomiting tended to be low compared with Group I, but the difference was not statistically significant. The incidence of pruritus was not different between the two groups in both early and late periods.

Aged↗

PubMed1999

The effects of a point mutation of the beta2 subunit of GABA(A) receptor on direct and modulatory actions of general anesthetics.

The gamma-aminobutyric acid type A receptor (GABA(A) receptor) sites involved in the direct and modulatory actions of general anesthetics remain to be elucidated. The mutation of tyrosine at position 157 in the beta2 GABA(A) receptor subunit was reported to reduce sensitivity to activation by GABA, but not pentobarbital. We examined whether this mutation of the beta2 subunit (Tyr157-->Phe) affects the direct and modulatory actions of other general anesthetics such as propofol and etomidate. Using the two-electrode voltage clamp method, we recorded Cl- current in Xenopus oocytes expressing alpha1beta2gamma2s and alpha1-mutated beta2gamma2s subunits. The mutation of the beta2 subunit reduced the apparent affinity for propofol. However, the mutation had no effect on both the direct actions of pentobarbital and etomidate or on the modulatory actions of pentobarbital, propofol and etomidate. These results suggest that unique loci may exist for the direct action of propofol and that the GABA binding site may not mediate the modulatory actions of general anesthetics at GABA(A) receptors.

Amino Acid Substitution↗

PubMed1999

Dynamic measurement of intrinsic PEEP does not represent the lowest intrinsic PEEP.

OBJECTIVE: Dynamic intrinsic PEEP (PEEPi-dyn) is the airway pressure required to overcome expiratory flow and is considered to represent the lowest regional PEEPi. However, there are few data to validate this assumption. We investigated if PEEPi-dyn represents the lowest PEEPi. SETTING: The animal laboratory at the Osaka University Medical School. MEASUREMENTS AND RESULTS: We compared static PEEPi (PEEPi-stat) and PEEPi-dyn in healthy animals. Five adult white rabbits (2.77+/-0.05 kg) were anesthetized, tracheostomized, and intubated with several different sizes of endotracheal tubes (ETT) (2.0, 2.5, 3.0, 3.5, or 4.0 mm i.d.). The animals were paralyzed and ventilated (Siemens Servo 900C). Baseline ventilator settings were at a rate of 50/min, inspiratory:expiratory (I:E) ratio of 2:1 or 4:1, and minute ventilation was manipulated to create 3 or 5 cm H2O PEEPi-stat. PEEPi-stat was measured using the expiratory hold button of the ventilator. PEEPi-dyn showed large variations. In all ventilator settings, PEEPi-dyn was higher than PEEPi-stat (p<0.001). The larger the ETT, the higher the PEEPi-dyn at an I:E ratio of 2:1 (p<0.05). The higher the minute ventilation, the greater the difference between PEEPi-stat and PEEPi-dyn. The tidal volume and the difference showed a significant correlation (r2 = 0.514, p<0.001). CONCLUSIONS: The value of PEEPi-dyn was dependent on ventilatory settings, and PEEPi-dyn does not necessarily represent the lowest regional PEEPi within the lungs.

Animals↗

PubMed1999

Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective Cesarean section.

BACKGROUND: The role of crystalloid preloading to prevent hypotension associated with spinal anesthesia in parturients during cesarean section has been challenged. Direct measurement of blood volume should provide insight regarding the volume-expanding effects. The aim of the current study was to clarify the effects of volume preload with either crystalloid or colloid solution on the changes in blood volume of parturients undergoing spinal anesthesia for cesarean section. METHODS: Thirty-six healthy parturients scheduled for elective cesarean section during spinal anesthesia were allocated randomly to one of three groups receiving 1.5 l lactated Ringer's solution (LR; n = 12), 0.5 l hydroxyethylstarch solution, 6% (0.5 l HES; n = 12), and 1.0 l hydroxyethylstarch solution, 6% (1.0 l HES; n = 12), respectively. Blood volume and cardiac output were measured before and after volume preloading with indocyanine green (ICG), and the indocyanine green blood concentrations were monitored by noninvasive pulse spectrophotometry. RESULTS: After volume preload, the blood volume significantly increased in all three groups (P < 0.01). The volume of infused solution remaining in the vascular space in the LR, 0.5-l HES, and 1.0-l HES groups were 0.43+/-0.20 l, 0.54+/-0.14 l, and 1.03+/-0.21 l, respectively, corresponding to 28% of lactated Ringer's solution and 100% of hydroxyethylstarch solution infused. Significant increases in cardiac output were observed in the 0.5-l and 1.0-l HES groups (P < 0.01). A significant correlation between the percentage increase in blood volume and that of cardiac output was observed by volume preloading (r2 = 0.838; P < 0.001). The incidence of hypotension was 75% for the LR group, 58% for the 0.5-l HES group, and 17% for the 1.0-l HES group, respectively. CONCLUSIONS: The incidence of hypotension developed in the 1.0-l HES group was significantly lower than that in the LR and 0.5-l HES groups, showing that greater volume expansion results in less hypotension. This result indicates that the augmentation of blood volume with preloading, regardless of the fluid used, must be large enough to result in a significant increase in cardiac output for effective prevention of hypotension.

Adult↗

PubMed1999

[Judicial judgements on anesthesia malpractice in Japan].

We reviewed 75 judicial precedents on anesthetic malpractice during surgical procedure which had appeared in legal journals in the period between 1963 and 1997. Anesthetic techniques employed were: general anesthesia (35 cases), spinal anesthesia (19 cases), local anesthesia (12 cases), and others (9 cases). Anesthesiologists were involved in 16 lawsuits, of which anesthesiologists lost 6 suits between 1986 and 1995. There were 8 cases classified as to be caused by respiratory problems including 2 cases of wrong gas supply. The defendants lost all the 8 cases. On the other hand, the plaintiff lost all the cases of malignant hyperthermia (n = 7). There is a tendency of increase in law suit with general anesthesia. Recent judgments suggested the importance of anesthetic managements, correct recording and appropriate monitoring by anesthesiologist during and immediately after surgery. Spinal anesthesia should be performed by anesthesiologist, and the frequency of anesthetic accident should be decreased. Japan is still in short of anesthesiologists and efforts should be paid to increase the number of anesthesia specialists.

Anesthesia↗

PubMed1998

Functional mapping of pain-related activation with echo-planar MRI: significance of the SII-insular region.

Activation in numerous regions of the brain is likely to be involved in the complex neural network function of pain perception. To detect the cortical representation during nonpainful and painful stimuli, which were presented using electrical finger stimulation in six normal right-handed male volunteers, we performed echo-planar functional magnetic resonance imaging (fMRI). Using a 1.5-T MR system that scanned the supratentorial region of the brain, we obtained multislice BOLD-based functional MR images with single-shot gradient-echo echo-planar imaging (EPI). The data show that dispersed brain regions are activated during painful stimulation, and especially demonstrate the significance of the SII-insular region in pain perception.

Adult↗

PubMed1998

Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model.

Intrathecal injection of a nitric oxide releasing compound, NOC-18, was used to define the role of nitric oxide (NO) in the spinal mechanism of neuropathic pain caused by unilateral chronic constriction injury to rat sciatic nerves. Paw withdrawal latency was used to evaluate nociception induced by thermal stimuli before surgery and afterwards at 1, 3, and 6 h, and on days 1, 2, 3, 4, 5, 8, and 12 after the nerve ligature. In the sham-surgery control groups, intrathecal injection of 10 or 100 microg of NOC-18 did not produce any change in withdrawal latencies. In rats with unilateral nerve ligation, however, administration of 1 or 10 microg, but not 0.1 microg, of NOC-18 significantly shortened the time in which thermal hyperalgesia developed after nerve injury. Injection of 1 microg of NOC-18 decreased the onset time of thermal hyperalgesia from 2 days to 3 h and with 10 microg hyperalgesia developed within 1 h after the nerve injury. The effects of intrathecal injection of MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, N-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, methylene blue (MB), a soluble guanylate cyclase inhibitor, and hemoglobin (Hb), a NO scavenger, on the development of thermal hyperalgesia after the sciatic nerve ligature were examined in the presence and absence of 1 and 10 microg of NOC-18. Acceleration of the development of thermal hyperalgesia induced by 1 and 10 microg NOC-18 was completely inhibited by Hb, but was not affected by either MK-801, L-NAME or MB. These findings indicate that NO plays an important role in the rapid development of thermal hyperalgesia after the nerve injury, but that facilitation of nociceptive processing in the spinal cord may entail an alternate to the NO-cyclic guanosine 3',5'-monophosphate (cGMP) pathway.

Animals↗

PubMed1998

Gamma subunit dependent modulation by nitric oxide (NO) in recombinant GABAA receptor.

The effect of nitric oxide (NO) on GABA induced Cl- current of recombinant GABAA receptors was studied. Either alpha 1 beta 2 gamma 2s or alpha 1 beta 2 subunit mRNAs synthesized from cDNA of mouse brain were injected into Xenopus oocytes and functional GABAA receptors were expressed. GABA-induced Cl- current was measured with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the GABA-induced Cl- current in the alpha 1 beta 2 gamma 2s subunit receptor in a dose-dependent manner. In alpha 1,beta 2 subunit receptor, NOC-18 had no effects on GABA-induced currents at low concentrations but showed potentiation at high concentration. These effects were antagonized by the NO extinguisher, carboxy-PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly acts at the GABAA receptor and the gamma 2s subunit is involved in its action.

Animals↗