Local Anesthetics Inhibit Transient Receptor Potential Vanilloid Subtype 3 Channel Function in Xenopus Oocytes.

BACKGROUND: The transient receptor potential vanilloid subtype 3 (TRPV3) channel is activated by innocuous temperature and several chemical stimuli. It is proposed to be involved in pathological pain development and is therefore considered a potential target for treating pain. Local anesthetics have been used for patients with both acute and chronic pain. Although blockage of the voltage-gated sodium channel is the primary mechanism by which local anesthetics exert their effects, they cannot be explained by this mechanism alone, especially in pathologic states such as chronic pain. Indeed, the effects of local anesthetics on multiple targets involved in the pain pathway have been reported. It has also been suggested that modulating the function of transient receptor potential (TRP) channels (eg, TRPV1 and transient receptor potential ankyrin 1 [TRPA1]) is one of the mechanisms of action of local anesthetics. However, the effects of local anesthetics on TRPV3 have not been reported. METHODS: We expressed TRPV3 in Xenopus oocytes and investigated the effects of local anesthetics on 2-aminoethoxydiphenyl borate (2APB)-induced currents using 2-electrode voltage-clamp techniques. RESULTS: Clinically used local anesthetics inhibited the 2APB-activated currents from the TRPV3 channel in a concentration-dependent manner at pharmacologically relevant concentrations with half maximal inhibitory concentration (IC50) values of 2.5 (lidocaine), 1.4 (mepivacaine), 0.28 (ropivacaine), and 0.17 (bupivacaine) mmol/L, respectively. Conversely, these local anesthetics also directly induced currents at higher concentrations, although these currents were quite small compared to the 2APB-induced currents. We found that the inhibition of TRPV3 by lidocaine is noncompetitive and independent of intracellular signaling cascades. 2APB-induced TRPV3 currents were reduced by extracellular N-(2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX-314) but not by intracellular QX-314 nor benzocaine. Moreover, lidocaine showed a use-dependent block in TRPV3 inhibition. Finally, QX-314 appeared to slightly permeate the activated TRPV3 channel pore based on examination of oocytes coexpressing TRPV3 and a sodium channel. These results suggest that local anesthetics could inhibit TRPV3 channel function by extracellular interactions of their charged forms with the channel pore. CONCLUSIONS: Local anesthetics inhibited TRPV3 2APB-induced currents at pharmacologically relevant concentrations when TRPV3 was expressed in Xenopus oocytes. These effects seem to occur via an extracellular interaction between the charged form of the anesthetic with the TRPV3 channel pore. These results help to elucidate the mechanisms of action of local anesthetics.

Carvacrol inhibits the neuronal voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.3, Nav1.7, and Nav1.8 expressed in Xenopus oocytes with different potencies.

Carvacrol is the predominant monoterpene in essential oils from many aromatic plants. Several animal studies showing analgesic effects of carvacrol indicate potential of carvacrol as a new medication for patients with refractory pain. Voltage-gated sodium channels (Nav) are thought to have crucial roles in the development of inflammatory and neuropathic pain, but there is limited information about whether the analgesic mechanism of carvacrol involves Nav. We used whole-cell, two-electrode, voltage-clamp techniques to examine the effects of carvacrol on sodium currents in Xenopus oocytes expressing α subunits of Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8. Carvacrol dose-dependently suppressed sodium currents at a holding potential that induced half-maximal current. The half-maximal inhibitory concentration values for Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 were 233, 526, 215, 367, and 824 µmol/L, respectively, indicating that carvacrol had more potent inhibitory effects towards Nav1.2 and Nav1.6 than Nav1.3, Nav1.7, and Nav1.8. Gating analysis showed a depolarizing shift of the activation curve and a hyperpolarizing shift of the inactivation curve in all five α subunits following carvacrol treatment. Furthermore, carvacrol exhibits a use-dependent block for all five α Nav subunits. These findings provide a better understanding of the mechanisms associated with the analgesic effect of carvacrol.

A novel method for evaluating activity of transient receptor potential channels using a cellular dielectric spectroscopy.

Cellular dielectric spectroscopy (CDS) is a novel technology enabling pharmacological evaluation of multiple receptor types with a label-free cell-based assay. We evaluated activities of a family of ligand-gated channels, transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels by an electrical impedance-based biosensor (CellKey™ system) using CDS. Measures of both potency (EC50) and efficacy (Emax) of these agonists with CellKey™ were almost identical to those made using the traditional Ca2+ influx assay in TRPV1- or TRPA1-expressing cells, suggesting that CellKey™ is a simpler and easier means of evaluating TRP activities.

Analysis of actual pressure point using the power flexible capacitive sensor during chest compression.

In chest compression for cardiopulmonary resuscitation (CPR), the lower half of the sternum is pressed according to the American Heart Association (AHA) guidelines 2010. These have been no studies which identify the exact location of the applied by individual chest compressions. We developed a rubber power-flexible capacitive sensor that could measure the actual pressure point of chest compression in real time. Here, we examined the pressure point of chest compression by ambulance crews during CPR using a mannequin. We included 179 ambulance crews. Chest compression was performed for 2 min. The pressure position was monitored, and the quality of chest compression was analyzed by using a flexible pressure sensor (Shinnosukekun™). Of the ambulance crews, 58 (32.4 %) pressed the center and 121 (67.6 %) pressed outside the proper area of chest compression. Many of them pressed outside the center; 8, 7, 41, and 90 pressed on the caudal, left, right, and cranial side, respectively. Average compression rate, average recoil, average depth, and average duty cycle were 108.6 counts per minute, 0.089, 4.5 cm, and 48.27 %, respectively. Many of the ambulance crews did not press on the sternal lower half definitely. This new device has the potential to improve the quality of CPR during training or in clinical practice.

A flexible pressure sensor could correctly measure the depth of chest compression on a mattress.

BACKGROUND: Feedback devices are used to improve the quality of chest compression (CC). However, reports have noted that accelerometers substantially overestimate depth when cardiopulmonary resuscitation (CPR) is performed on a soft surface. Here, we determined whether a flexible pressure sensor could correctly evaluate the depth CC performed on a mannequin placed on a mattress. METHODS: Chest compression was performed 100 times/min by a compression machine on the floor or a mattress, and the depth of CC was monitored using a flexible pressure sensor (Shinnosukekun) and CPRmeter(™). The depth of machine-performed CC was consistently 5cm. We compared data from the feedback sensor with the true depth of CC using dual real-time auto feedback system that incorporated an infrared camera (CPR evolution(™)). RESULTS: On the floor, the true depth of CC was 5.0±0.0cm (n=100), or identical to the depth of CC performed by the machine. The Shinnosukekun(™) measured a mean (±SD) CC depth of 5.0±0.1cm (n=100), and the CPRmeter(™) measured a depth of 5.0±0.2cm (n=100). On the mattress, the true depth of CC was 4.4±0.0cm (n=100). The Shinnosukekun(™) measured a mean CC depth of 4.4±0.0cm (n=100), and the CPRmeter(™) measured a depth of 4.7±0.1cm (n=100). The data of CPRmeter(™) were overestimated (P<.0001 between the true depth and the CPRmeter(™)-measured depth). CONCLUSION: The Shinnosukekun(™) could correctly measure the depth of CC on a mattress. According to our present results, the flexible pressure sensor could be a useful feedback system for CC performed on a soft surface.

Tramadol and its metabolite m1 selectively suppress transient receptor potential ankyrin 1 activity, but not transient receptor potential vanilloid 1 activity.

BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1), which are expressed in sensory neurons, are polymodal nonselective cation channels that sense noxious stimuli. Recent reports showed that these channels play important roles in inflammatory, neuropathic, or cancer pain, suggesting that they may serve as attractive analgesic pharmacological targets. Tramadol is an effective analgesic that is widely used in clinical practice. Reportedly, tramadol and its metabolite (M1) bind to µ-opioid receptors and/or inhibit reuptake of monoamines in the central nervous system, resulting in the activation of the descending inhibitory system. However, the fundamental mechanisms of tramadol in pain control remain unclear. TRPV1 and TRPA1 may be targets of tramadol; however, they have not been studied extensively. METHODS: We examined whether and how tramadol and M1 act on human embryonic kidney 293 (HEK293) cells expressing human TRPV1 (hTRPV1) or hTRPA1 by using a Ca imaging assay and whole-cell patch-clamp recording. RESULTS: Tramadol and M1 (0.01-10 µM) alone did not increase in intracellular Ca concentration ([Ca]i) in HEK293 cells expressing hTRPV1 or hTRPA1 compared with capsaicin (a TRPV1 agonist) or the allyl isothiocyanate (AITC, a TRPA1 agonist), respectively. Furthermore, in HEK293 cells expressing hTRPV1, pretreatment with tramadol or M1 for 5 minutes did not change the increase in [Ca]i induced by capsaicin. Conversely, pretreatment with tramadol (0.1-10 µM) and M1 (1-10 µM) significantly suppressed the AITC-induced [Ca]i increases in HEK293 cells expressing hTRPA1. In addition, the patch-clamp study showed that pretreatment with tramadol and M1 (10 µM) decreased the inward currents induced by AITC. CONCLUSIONS: These data indicate that tramadol and M1 selectively inhibit the function of hTRPA1, but not that of hTRPV1, and that hTRPA1 may play a role in the analgesic effects of these compounds.

µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1).

Tramadol has been used as an analgesic for several decades. µ-Opioid receptors (µORs) are the major receptors that mediate the analgesic effects of opioids. Although µORs have been thought to be one of the sites of action of tramadol, there has been no report that directly proves whether tramadol is an agonist of µOR or not. In this study, we examined the effects of tramadol and its main active metabolite O-desmethyltramadol (M1), on the function of µORs using Xenopus oocytes expressing cloned human µORs. The effects of tramadol and M1 were evaluated using the Ca(2+)-activated Cl(-) current assay method for G(i/o)-protein-coupled receptors by using a µOR fused to G(qi5) (µOR-G(qi5)) in Xenopus oocytes. DAMGO [(D-Ala(2), N-MePhe(4), Gly(5)-ol)-enkephalin] evoked Cl(-) currents in oocytes expressing µOR-G(qi5) in a concentration-dependent manner. Tramadol and M1 also evoked Cl(-) currents in the oocytes expressing µOR-G(qi5); however, relatively higher concentrations (compared to DMAGO) were necessary to induce such currents. Tramadol and M1 had a direct effect on µORs expressed in Xenopus oocytes. Although the monoamine uptake system and several types of ligand-gated ion channels are thought to be one of the targets for tramadol, tramadol-induced antinociception may be mediated at least in part, by the direct activation of µORs.

The recent progress in research on effects of anesthetics and analgesics on G protein-coupled receptors.

The exact mechanisms of action behind anesthetics and analgesics are still unclear. Much attention was focused on ion channels in the central nervous system as targets for anesthetics and analgesics in the 1980s. During the 1990s, major advances were made in our understanding of the physiology and pharmacology of G protein coupled receptor (GPCR) signaling. Thus, several lines of studies have shown that G protein coupled receptors (GPCRs) are one of the targets for anesthetics and analgesics and especially, that some of them inhibit the functions of GPCRs, i.e,, muscarinic receptors and substance P receptors. However, these studies had been focused on only G(q) coupled receptors. There has been little work on G(s)- and G(i)-coupled receptors. In the last decade, a new assay system, using chimera G(i/o)-coupled receptor fused to Gq(i5), has been established and the effects of anesthetics and analgesics on the function of G(i)-coupled receptors is now more easily studied. This review highlights the recent progress of the studies regarding the effects of anesthetics and analgesics on GPCRs.

The tramadol metabolite O-desmethyl tramadol inhibits substance P-receptor functions expressed in Xenopus oocytes.

Tramadol has been widely used as analgesic. O-Desmethyl tramadol (ODT) is one of the main metabolites of tramadol, having much greater analgesic potency than tramadol itself. Substance P receptors (SPR) are well known to modulate nociceptive transmission within the spinal cord. In this study, we investigated the effects of ODT on SPR expressed in Xenopus oocytes by examining SP-induced Ca(2+)-activated Cl(-) currents. ODT inhibited the SPR-induced Cl(-) currents at pharmacologically relevant concentrations. The protein kinase C (PKC) inhibitor bisindolylmaleimide I did not abolish the inhibitory effects of ODT on SP-induced Ca(2+)-activated Cl(-) currents. The results suggest that the tramadol metabolite ODT inhibits the SPR functions, which may be independent of activation of PKC-mediated pathways.

Sevoflurane inhibits the µ-opioid receptor function expressed in Xenopus oocytes.

Sevoflurane is widely used for anesthesia, and is commonly used together with opioids in clinical practice. However, the effects of sevoflurane on µ-opioid receptor (µOR) functions is still unclear. In this study, the effects of sevoflurane on µOR functions were analyzed by using Xenopus oocytes expressing a µOR fused to chimeric Gα protein G(qi5) (µOR-G(qi5)). Sevoflurane by itself did not elicit any currents in oocytes expressing µOR-G(qi5), whereas sevoflurane inhibited the [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO)-induced Cl(-) currents at clinically used concentrations. Sevoflurane did not affect the Cl(-) currents induced by AlF(4)(-), which directly led to activation of G proteins. The inhibitory effects of sevoflurane on the DAMGO-induced currents were not observed in oocytes pretreated with the protein kinase C (PKC) inhibitor GF109203X. These findings suggest that sevoflurane would inhibit µOR function. Further, the mechanism of inhibition by sevoflurane would be mediated by PKC.

Effects of sevoflurane on voltage-gated sodium channel Na(v)1.8, Na(v)1.7, and Na(v)1.4 expressed in Xenopus oocytes.

Sevoflurane is widely used as a volatile anesthetic in clinical practice. However, its mechanism is still unclear. Recently, it has been reported that voltage-gated sodium channels have important roles in anesthetic mechanisms. Much attention has been paid to the effects of sevoflurane on voltage-dependent sodium channels. To elucidate this, we examined the effects of sevoflurane on Na(v) 1.8, Na(v) 1.4, and Na(v) 1.7 expressed in Xenopus oocytes. The effects of sevoflurane on Na(v) 1.8, Na(v) 1.4, and Na(v) 1.7 sodium channels were studied by an electrophysiology method using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. Sevoflurane at 1.0 mM inhibited the voltage-gated sodium channels Na(v)1.8, Na(v)1.4, and Na(v)1.7, but sevoflurane (0.5 mM) had little effect. This inhibitory effect of 1 mM sevoflurane was completely abolished by pretreatment with protein kinase C (PKC) inhibitor, bisindolylmaleimide I. Sevoflurane appears to have inhibitory effects on Na(v)1.8, Na(v)1.4, and Na(v) 1.7 by PKC pathways. However, these sodium channels might not be related to the clinical anesthetic effects of sevoflurane.

Analysis of the effects of anesthetics and ethanol on mu-opioid receptor.

G protein-coupled receptors, in particular, Ca(2+)-mobilizing G(q)-coupled receptors have been reported to be targets for anesthetics. Opioids are commonly used analgesics in clinical practice, but the effects of anesthetics on the opioid mu-receptors (muOR) have not been systematically examined. We report here an electrophysiological assay to analyze the effects of anesthetics and ethanol on the functions of muOR in Xenopus oocytes expressing a muOR fused to chimeric Galpha protein G(qi5) (muOR-G(qi5)). Using this system, the effects of halothane, ketamine, propofol, and ethanol on the muOR functions were analyzed. In oocytes expressing muOR-G(qi5), the( )muOR agonist DAMGO ([D-Ala(2),N-MePhe(4),Gly-ol]-enkephalin) elicited Ca(2+)-activated Cl(-) currents in a concentration-dependent manner (EC(50) = 0.24 microM). Ketamine, propofol, halothane, and ethanol themselves did not elicit any currents in oocytes expressing muOR-G(qi5), whereas ketamine and ethanol inhibited the DAMGO-induced Cl(-) currents at clinically equivalent concentrations. Propofol and halothane inhibited the DAMGO-induced currents only at higher concentrations. These findings suggest that ketamine and ethanol may inhibit muOR functions in clinical practice. We propose that the electrophysiological assay in Xenopus oocytes expressing muOR-G(qi5) would be useful for analyzing the effects of anesthetics and analgesics on opioid receptor function.

[Screening of sleep apnea syndrome with Sleeprecorder SD-101].

Polysomnography (PSG) has been the gold standard for the diagnosis of sleep apnea syndrome (SAS). However, PSG is not generally available since it is technically demanding, and cost and labour are necessary. Currently, there is growing demand for its diagnosis. Thus, simplified portable equipments have been increasingly utilized. Sleeprecorder SD-101 (Suzuken, Nagoya, Japan) is a pad-shaped and novel device for SAS analysis. A total of 162 sitting-sensor tips are 1.6 inch apart, embeded in the 55 x 22 inch pad, and capable of detecting load with precision of one gram. Sleeprecorder SD-101 placed beneath the chest can recognize respiratory pattern and record thoracic movement during sleep. SASLyzer (Suzuken, Nagoya, Japan), a software installed in a compatible PC, analyzes the data and indicates apnea-hypopnea index (AHI). We present a case of SAS in a 40-year-old man (181 cm, 98 kg) with peritonsillitis. We used Sleeprecorder SD-101 since he complained of severe snoring and excessive daytime sleepiness. He had severe SAS with AHI 50.7. Subsequently, conventional PSG also indicated AHI 77. In the present case with severe SAS, these two methods showed equivalent severity. Sleeprecorder SD-101 could be a useful device for screening of SAS patients.

[Anesthesia in a patient with alkaptonuric ochronosis for total hip arthroplasty].

Alkaptonuric ochronosis, caused by a deficiency of homogentisate 1,2-dioxygenase, is a rare, autosomal recessive, metabolic disorder. Accumulation of homogentisate acid (HGA) at the connective tissue destructs the spine and large joints, and cardiac valvular disease is prominent. In this report, we describe a case of alkaptonuric ochronosis for anesthetic management. A 75-year-old female patient with the disease was scheduled for a total-hip arthroplasty. We avoided applying general anesthesia for her valvular regurgitations. Spinal anesthesia was achieved successfully, and resulted in a hypesthesia level at T12. Although a epidural catheter was indwelled with no leak of cerebrospinal fluid, an accidental dural puncture appeared later during the surgery, suggesting a subdural catheterization. She had an uneventful perioperative course without any symptoms. In the patient of alkaptonuric ochronosis, the dura and arachnoid membrane could be damaged made vulnerable by HGA. In addition, since the clinical findings resemble ankylosing spondylitis, degenerative changes such as a narrowing of the disk space and spine fusion would make the regional technique unsuccessful. In term of anesthesia, alkaptonuric ochronosis requires ingenuity since there are a number of factors associated with prevention of untoward complications. Each case is to be evaluated individually and managed carefully.

Modulation of synaptic inputs in magnocellular neurones in a rat model of cancer cachexia.

In cancer cachexia, abnormal metabolism and neuroendocrine dysfunction cause anorexia, tissue damage and atrophy, which can in turn alter body fluid balance. Arginine vasopressin, which regulates fluid homeostasis, is secreted by magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus. Arginine vasopressin secretion by MNCs is regulated by both excitatory and inhibitory synaptic activity, alterations in plasma osmolarity and various peptides, including angiotensin II. In the present study, we used whole-cell patch-clamp recordings of brain slices to determine whether hyperosmotic stimulation and/or angiotensin II potentiate excitatory synaptic input in a rat model of cancer cachexia, similar to their effects in normal (control) rats. Hyperosmotic (15 and 60 mmol L-1   mannitol) stimulation and angiotensin II (0.1 µmol L-1 ) increased the frequency, but not the amplitude, of miniature excitatory postsynaptic currents in normal rats; in model rats, both effects were significantly attenuated. These results suggest that cancer cachexia alters supraoptic MNC sensitivity to osmotic and angiotensin II stimulation.

Dexmedetomidine inhibits muscarinic type 3 receptors expressed in Xenopus oocytes and muscarine-induced intracellular Ca2+ elevation in cultured rat dorsal root ganglia cells.

Dexmedetomidine, an alpha(2)-adrenoceptor agonist, has been approved for clinical use, although the mechanism of dexmedetomidine action has not been fully elucidated. Several studies have shown that G protein-coupled receptors (GPCRs) are recognized as targets for anesthetics and analgesics. Therefore, it is of interest to determine whether dexmedetomidine affects the function of GPCRs other than the alpha(2)-adrenoceptor. We examined the effects of dexmedetomidine on M(1), M(3), 5-HT(2C), substance P, and orexin 1 receptors in Xenopus oocytes expressing individual receptors. In addition, we investigated the effects of dexmedetomidine on muscarinic receptor-mediated changes in [Ca(2+)](i) in the dorsal root ganglia (DRG) of 3-week-old Wister rats. Dexmedetomidine did not affect the 5-HT(2C)-, or substance P-induced Cl(-) currents and had little inhibition on the orexin A-induced current in oocytes expressing the respective receptors. The compound also had little effect on the acetylcholine (ACh, 1 microM)-induced Ca(2+)-activated Cl(-) currents in Xenopus oocytes expressing M(1) receptors. In contrast, dexmedetomidine inhibited the ACh-induced currents in Xenopus oocytes expressing M(3) receptors; 1 nM, 10 nM, 100 nM, and 1 microM dexmedetomidine reduced the current to 66.5 +/- 4.8, 51.3 +/- 12, 34.6 +/- 11, and 26.8 +/- 6.4% of the control value, respectively (EC(50) = 3.5 +/- 0.7 nM). Dexmedetomidine reduced the ACh-induced Cl(-) currents after treatment with the selective protein kinase C inhibitor GF109203X. Moreover, the compound inhibited the muscarinic receptor-mediated increases in [Ca(2+)](i) in cultured DRG cells in a concentration-dependent manner. Dexmedetomidine inhibits the function of M(3) receptors, in addition to its agonistic effects on alpha(2)-adrenoceptors, which provides further insight into the pharmacological properties of dexmedetomidine.

[Effects of colforsin daropate hydrochloride on myocardium, smooth muscle and renal function].

In the failing heart, numerous changes occur in cardiac adrenergic receptors (ARs) and intracellular signal transduction pathways. The most striking of these alterations appears at beta1 ARs, and the desensitization is the most prominent. Since malfunctions of beta1 ARs prevent intracellular signal transduction, the desensitization plays an important role in the onset and progression of the heart failure. Currently, several lines of evidence show the efficacy of inotropic agents, such as adenylate cyclase activator, that depend not on the ARs. Thus, it is essential to understand the pathway for the etiologic/pathologic evaluation for appropriate usage of these drugs for an adequate period. A novel water-soluble forskolin derivative, colforsin daropate hydrochloride (CDH) is a positive inotropic agent for treatment of the heart failure, especially in the severe stage with the beta1 AR desensitization. CDH potentiates cAMP activity via its direct action on adenylate cyclase, resulting in cardiotonic action. On the other hand, CDH relaxes vascular smooth muscle, while it antagonizes antidiuretic effects of angiotensin II and noradrenaline, involved in renal protection. In addition, CDH attenuates the mesangial cell proliferation and the inflammatory reaction, related with antiproliferative property of adrenomedullin and ketamine. To gain insights into the CDH action, we should take into account that intracellular signal transduction pathways in myocardium, smooth muscle and mesangial cell are controlled in a distinct manner.

Gq protein-coupled receptors as targets for anesthetics.

The mechanisms of action of anesthetics are unclear. Much attention has been focused on ion channels in the central nervous system as targets for anesthetics. During the last decade, major advances have been made in our understanding of the physiology and pharmacology of G-protein-coupled receptor (GPCR) signaling. Several lines of studies have shown that GPCRs are targets for anesthetics and that some anesthetics inhibit the functions of Gq-coupled receptors, including muscarinic acetylcholine (ACh) M(1), metabotropic type 5 glutamate, 5-hydroxytryptamine (5-HT) type 2A, and substance P receptors. Nearly 160 GPCRs have been identified, based on their gene sequence and ability to interact with known endogenous ligands. However, an estimated 500-800 additional GPCRs have been classified as "orphan" receptors (oGPCRs) because their endogenous ligands have not yet been identified. Given that known GPCRs are targets for anesthetics, these oGPCRs represent a rich group of receptor targets for anesthetics. This article highlights the effects of anesthetics on Gq-coupled receptors, and discusses whether GPCRs other than Gq-coupled receptors are targets for anesthetics.

[Anesthesia for a patient with polyarteritis nodosa who has a history of multiple drug allergies].

There has been little information about anesthesia for a patient with a history of multiple drug allergies. We gave anesthesia for a 32-year-old woman with polyarteritis nodosa and history of multiple drug allergies. She was scheduled to undergo bilateral tonsilectomy. We could not perform the preoperative screening of the drugs using a dermal test because of a high risk of anaphylactic shock. Anesthesia was induced with sevoflurane and nitrous oxide and maintained with sevoflurane, nitrous oxide, and fentanyl. The intra- and postoperative course was uneventful. It is important to inquire history of allergies adequately for preoperative recognition of allergens. General anesthesia with sevoflurane would be useful for a patient with history of multiple drug allergies.