著者

Ryosuke Tanaka Junji Takayama Masanori Takaoka Yohko Sugino Mamoru Ohkita Yasuo Matsumura

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.126, no.3, pp.291-291, 2014 (Released:2014-11-20)

著者

Yoshihiro Uesawa Shigeru Hishinuma Masaru Shoji

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.124, no.2, pp.160-168, 2014-02-20 (Released:2014-02-19)

参考文献数

28

被引用文献数

3 6

---

There is argument whether non-sedative properties of histamine H1–receptor antagonists (antihistamines) are determined by their active extrusions from the brain via P-glycoprotein or their restricted penetration through the blood-brain barrier. We have reported that sedative and non-sedative antihistamines can be well discriminated by measuring changes in their binding to H1 receptors upon receptor internalization in intact cells, which depends on their membrane-penetrating ability. In this study, molecular determinants responsible for sedative and non-sedative properties of antihistamines were evaluated by quantitative structure-activity relationship (QSAR) analyses. Multiple regression analyses were applied to construct a QSAR model, taking internalization-mediated changes in the binding of antihistamines as objective variables and their structural descriptors as explanatory variables. The multiple regression model was successfully constructed with two explanatory variables, i.e., lipophilicity of the compounds at physiological pH (logD) and mean information content on the distance degree equality (IDDE) (r2 = 0.753). The constructed model discriminated between sedative and non-sedative antihistamines with 94% accuracy for external validation. These results suggest that logD and IDDE concerning lipophilicity and molecular shapes of compounds, respectively, predominantly determine the membrane-penetrating ability of antihistamines for their side effects on the central nervous system.

著者

Takeo Kubota Kunio Miyake Takae Hirasawa Kaoru Nagai Tsuyoshi Koide

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.113, no.1, pp.3-8, 2010 (Released:2010-05-17)

参考文献数

66

被引用文献数

6 8

---

Epigenetics is a mechanism that regulates gene expression not depending on the underlying DNA sequence, but on the chemical modifications of DNA and histone proteins. Defects in the factors involved in epigenetic regulation cause congenital neurodevelopmental diseases, and thus, epigenetic regulation is essential for normal brain development. Besides these intrinsic defects, it is becoming increasingly apparent that extrinsic factors, such as insufficient nutrition, psychiatric drugs, and mental stress, also alter epigenetic regulation. Therefore, environmental factors may lead to “acquired” neurodevelopmental disorders through the failure of epigenetic regulation. Epigenetics is a biological key to understand the gene–environment interactions in neurodevelopmental disorders. As the mechanism is reversible, its comprehensive understanding will result in the development of new therapies for these disorders.

著者

斉藤 貴志 西道 隆臣

出版者

(公社)日本薬理学会

雑誌

日本薬理学雑誌 (ISSN:00155691)

巻号頁・発行日

vol.144, no.5, pp.250-252, 2014 (Released:2014-11-10)

参考文献数

10

被引用文献数

1

著者

William K.K. Wu Chi Hin Cho

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.94, no.4, pp.348-358, 2004 (Released:2004-04-20)

参考文献数

105

被引用文献数

22 46

---

Increasing use of tobacco and its related health problems are a great concern in the world. Recent epidemiological findings have demonstrated the positive association between cigarette smoking and several gastrointestinal (GI) diseases, including peptic ulcer and cancers. Interestingly, smoking also modifies the disease course of ulcerative colitis (UC). Nicotine, a major component of cigarette smoke, seems to mediate some of the actions of cigarette smoking on the pathogenesis of GI disorders. Nicotine worsens the detrimental effects of aggressive factors and attenuates the protective actions of defensive factors in the processes of development and repair of gastric ulceration. Nicotine also takes part in the initiation and promotion of carcinogenesis in the GI tract. In this regard, nicotine and its metabolites are found to be mutagenic and have the ability to modulate cell proliferation, apoptosis, and angiogenesis during tumoriogenesis through specific receptors and signalling pathways. However, to elucidate this complex pathogenic mechanism, further study at the molecular level is warranted. In contrast, findings of clinical trials give promising results on the use of nicotine as an adjuvant therapy for UC. The beneficial effect of nicotine on UC seems to be mediated through multiple mechanisms. More clinical studies are needed to establish the therapeutic value of nicotine in this disease.

著者

Yu Ohmura Emily M. Jutkiewicz Mitsuhiro Yoshioka Edward F. Domino

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.117, no.2, pp.121-124, 2011 (Released:2011-10-17)

参考文献数

15

被引用文献数

6 16

---

Abrupt nicotine cessation after chronic use disrupts monoaminergic systems and causes withdrawal signs/symptoms. In this study, the precursor of serotonin 5-hydroxytryptophan (5-HTP) relieved nicotine withdrawal signs. (−)-Nicotine bitartrate or equimolar sodium tartrate was infused into each rat via a s.c. osmotic minipump for 7 days. Somatic abstinence signs (teeth-chattering/chews and shakes, etc.) were counted one day after pump removal. Somatic signs were attenuated by the i.p. injection of 5-HTP, but not by NSD-1015, a centrally-acting L-aromatic amino acid decarboxylase inhibitor, indicating that 5-HTP mitigates somatic signs mainly through its conversion to 5-HT.

著者

Eri Tsukagoshi Mitsuru Kawaguchi Takashi Shinomiya Masanobu Yoshikawa Toshihiko Kawano Migiwa Okubo Kohei Sawaki

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.115, no.2, pp.221-229, 2011 (Released:2011-02-18)

参考文献数

32

被引用文献数

3 8 4

---

Peripheral-type benzodiazepine receptor (PBR) and central-type benzodiazepine receptor (CBR) in salivary gland play a role in the inhibitory regulation of salivary secretion in rodents. Diazepam-binding inhibitor (DBI), an endogenous ligand for PBR, produces neurosteroids, which modulate CBR activity. In this study, we investigated the effect of repetitive administration of diazepam (DZP) on salivary secretion and expression of DBI mRNA and peptide. Moreover, mRNA expression of PBR and pituitary adenylate cyclase–activating polypeptide (PACAP), a transcriptional regulator for DBI promoter, was evaluated after repetitive administration of DZP. Repetitive administration, but not single administration, of 0.4 mg/kg DZP caused inhibition of salivary secretion and enhanced expression of DBI, PACAP, and PBR mRNA in rat salivary gland, with an increase in production of DBI peptide. These results suggest that repetitive administration of DZP stimulates DBI production, which may result in an increase in the suppressive effect of DZP on salivary secretion.

著者

Keita Mizuno Toru Kono Yasuyuki Suzuki Chika Miyagi Yuji Omiya Kanako Miyano Yoshio Kase Yasuhito Uezono

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.13244FP, (Released:2014-04-29)

参考文献数

40

被引用文献数

9 43

---

The acute peripheral neuropathy induced by oxaliplatin treatment occurs very frequently and is aggravated by exposure to cold. Goshajinkigan (GJG), a traditional Japanese (kampo) medicine, was recently shown to be effective against oxaliplatin-induced acute neuropathy. However, because the effects of GJG and its mechanism in relation to those of its ingredients and its mechanism are not well understood, we examined the effects of GJG on acute neuropathy. Further, we investigated whether GJG affects the functions and gene expressions of transient receptor potential (TRP) channels using a rat model of oxaliplatin-induced neuropathy. Administration of oxaliplatin increased withdrawal responses from cold stimulation, and GJG or calcium gluconate/magnesium sulfate significantly inhibited the oxaliplatin-induced cold hypersensitivity. Application of menthol, a TRPA1/TRPM8 agonist, or allyl isothiocyanate (AITC), a selective TRPA1 agonist, to the hind paw of oxaliplatin-treated rats enhanced the nocifensive behaviors evoked by each agonist, whereas oxaliplatin had no significant effect on nocifensive behaviors evoked by capsaicin, a TRPV1 agonist. GJG treatment reduced menthol- or AITC-evoked withdrawal responses potentiated by oxaliplatin. Furthermore, GJG suppressed the increase of TRPA1 and TRPM8 mRNA expression induced by oxaliplatin in dorsal root ganglia. These findings suggest that GJG prevented oxaliplatin-induced acute peripheral neuropathy by suppressing functional alteration of TRP channels, especially TRPA1 and TRPM8.

著者

Golmaryam Sarlak Anorut Jenwitheesuk Banthit Chetsawang Piyarat Govitrapong

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.123, no.1, pp.9-24, 2013-09-20 (Released:2013-09-20)

参考文献数

231

被引用文献数

23 62

---

Neural aging as a progressive loss of function involves central and peripheral post-mitotic neurons and neural stem cells (NSCs). It promotes neurodegeneration, impairs neurogenesis, and can be considered a cause of cognitive impairment and sensory and motor deficits in the elderly. Age-related morphological atrophic changes and cellular alterations are addressed by neural aging mechanisms. Neurogenesis declines during aging through several mechanisms such as an increase in quiescence state, changes in lineage fate, telomerase dysfunction, the failure of the DNA repair system, increased apoptosis, and the impairment of self-renewal. The self-renewal transcriptional factor Sox2 has been correlated with retrotransposon L1 and certain cell-cycle– and epigenetic-related factors, which are sometimes considered age-related factors in NSC aging. As neurogenesis decreases, non-mitotic neurons undergo neurodegeneration by oxidative stress, sirtuin, insulin signaling and mTOR alteration, mitochondrial dysfunction, and protein misfolding and aggregation. As neurodegeneration and impaired neurogenesis promote the nervous system aging process, the identification of neuronal anti-aging is required to raise life expectancy. The role of melatonin in increasing neurogenesis and protecting against neurodegeneration has been investigated. Here, we review nervous system aging that is correlated with mechanisms of neurodegeneration and the impairment of neurogenesis and evaluate the effects of melatonin on these processes.

著者

Eun-Joo Shin Jae-Hyung Bach Sung Youl Lee Jeong Min Kim Jinhwa Lee Jau-Shyong Hong Toshitaka Nabeshima Hyoung-Chun Kim

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.116, no.2, pp.137-148, 2011 (Released:2011-06-16)

参考文献数

100

被引用文献数

11 28

---

Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic, this review focuses on the neuroprotective effects of dextromethorphan and its analogs. Some of these analogs, particularly dimemorfan (3-methyl-17-methylmorphinan) and 3-hydroxymorphinan, have promising neuroprotective properties with negligible neuropsychotoxic effects. Their neuroprotective effects, the mechanisms underlying these effects, and their therapeutic potential for the treatment of diverse neurodegenerative disorders are discussed.

著者

Takuya Hirata Yoshihiro Keto Toshiyuki Funatsu Shinobu Akuzawa Masao Sasamata

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.104, no.3, pp.263-273, 2007 (Released:2007-07-24)

参考文献数

34

被引用文献数

15 35

---

We examined the pharmacological profile of ramosetron, a 5-HT3-receptor antagonist for irritable bowel syndrome with diarrhea, comparing it with those of other 5-HT3-receptor antagonists, alosetron and cilansetron, and the anti-diarrheal agent loperamide. Ramosetron showed high affinity for cloned human and rat 5-HT3 receptors, with Ki values of 0.091 ± 0.014 and 0.22 ± 0.051 nmol/L, respectively, while its affinities for other receptors, transporters, ion channels, and enzymes were negligible. Dissociation of ramosetron from the human 5-HT3 receptor was extremely slow (t1/2 = 560 min), while alosetron (t1/2 = 180 min) and cilansetron (t1/2 = 88 min) dissociated relatively rapidly. Ramosetron competitively inhibited 5-HT-induced contraction of isolated guinea-pig colon, with pA2 values of 8.6 (8.5 – 9.0). Ramosetron given orally also dose-dependently inhibited the von Bezold-Jarisch reflex in rats, with an ED50 value of 1.2 (0.93 – 1.6) μg/kg. In addition, oral ramosetron dose-dependently inhibited restraint stress-induced defecation in rats, with an ED50 value of 0.62 (0.17 – 1.2) μg/kg. In all of these experiments, the potencies of ramosetron were greater than those of alosetron, cilansetron, or loperamide. These results indicate that ramosetron is a highly potent and selective 5-HT3-receptor antagonist, with beneficial effects against stress-induced abnormal defecation in rats.

著者

Gu Kang Pil-Jae Kong Young-Jin Yuh So-Young Lim Sung-Vin Yim Wanjoo Chun Sung-Soo Kim

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.94, no.3, pp.325-328, 2004 (Released:2004-03-20)

参考文献数

17

被引用文献数

69 139

---

Inflammation is a significant component of chronic neurodegenerative diseases. Cyclooxygenase-2 (COX-2) is expressed in activated microglial cells and appears to be an important source of prostaglandins during inflammatory conditions. To investigate the effect of curcumin on COX-2 gene expression in microglial cells, we treated lipopolysaccharide (LPS)-challenged BV2 microglial cells with various concentrations of curcumin. Curcumin significantly inhibited LPS-mediated induction of COX-2 expression in both mRNA and protein levels in a concentration-dependent manner. COX-2 enzyme activity was also inhibited in accordance with mRNA and protein levels. Furthermore, curcumin markedly inhibited LPS-induced nuclear factor κB (NF-κB) and activator protein 1 (AP-1) DNA bindings. These data suggest that curcumin suppresses LPS-induced COX-2 gene expression by inhibiting NF-κB and AP-1 DNA bindings in BV2 microglial cells.

著者

Hiroshi Ujike Yukitaka Morita

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.96, no.4, pp.376-381, 2004 (Released:2004-12-22)

参考文献数

34

被引用文献数

39 63

---

Cannabis consumption may induce psychotic states in normal individuals, worsen psychotic symptoms of schizophrenic patients, and may facilitate precipitation of schizophrenia in vulnerable individuals. Recent studies provide additional biological and genetic evidence for the cannabinoid hypothesis of schizophrenia. Examinations using [3H]CP-55940 or [3H]SR141716A revealed that the density of CB1 receptors, a central type of cannabinoid receptor, is increased in subregions of the prefrontal cortex in schizophrenia. Anandamide, an endogenous cannabinoid, is also increased in the CSF in schizophrenia. A genetic study revealed that the CNR1 gene, which encodes CB1 receptors, is associated with schizophrenia, especially the hebephrenic type. Individuals with a 9-repeat allele of an AAT-repeat polymorphism of the gene may have a 2.3-fold higher susceptibility to schizophrenia. Recent findings consistently indicate that hyperactivity of the central cannabinoid system is involved in the pathogenesis of schizophrenia or the neural mechanisms of negative symptoms.

著者

Tsuneyuki Yamamoto Kusnandar Anggadiredja Takato Hiranita

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.96, no.4, pp.382-388, 2004 (Released:2004-12-22)

参考文献数

51

被引用文献数

16 23

---

Growing evidence on the involvement of cannabinoids in the rewarding effects of various kinds of drugs of abuse has suggested that not only the classical dopaminergic and opioidergic, but also the most recently established endocannabinoid system is implicated in the brain reward system. Furthermore, the interplay between the three systems has been shown to be an essential neural substrate underlying many aspects of drug addiction including craving and relapse. Relapse, the resumption of drug taking following a period of drug abstinence, is considered the main hurdle in treating drug addiction. Yet, little is known about its underlying mechanisms. The link between the endocannabinoid system and the arachidonic cascade is currently being clarified. While several findings have, indeed, shown the essential role of the endocannabinoid system in the reinstatement model, the endocannabinoid-arachidonic acid pathway may also be an important part in the neural machinery underlying relapse. This evidence may provide an alternative approach that will open a novel strategy in combating drug addiction.

著者

Atsushi Usami Takuya Sasaki Nobuhiro Satoh Takahiro Akiba Satoshi Yokoshima Tohru Fukuyama Kenzo Yamatsugu Motomu Kanai Masakatsu Shibasaki Norio Matsuki Yuji Ikegaya

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.106, no.4, pp.659-662, 2008 (Released:2008-04-19)

参考文献数

15

被引用文献数

24 33

---

Oseltamivir, a widely used anti-influenza drug, inhibits virus neuraminidase. A mammalian homologue of this enzyme is expressed in the brain, yet the effect of oseltamivir on central neurons is largely unknown. Patch-clamp recordings ex vivo revealed that oseltamivir enhanced spike synchronization between hippocampal CA3 pyramidal cells. Time-lapse multineuron calcium imaging revealed that oseltamivir and its active metabolite evoked synchronized population bursts that recruited virtually all neurons in the network. This unique, so-far-unknown, event was attenuated by muscarinic receptor antagonist. Thus, oseltamivir is a useful tool for investigating a new aspect of neural circuit operation.

著者

Taizo Kita George C. Wagner Toshikatsu Nakashima

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.92, no.3, pp.178-195, 2003 (Released:2003-07-23)

参考文献数

161

被引用文献数

95 134 169

---

Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson’s disease.

著者

Michio Hashimoto Motoko Maekawa Masanori Katakura Kei Hamazaki Yutaka Matsuoka

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.124, no.3, pp.294-300, 2014-03-20 (Released:2014-03-18)

参考文献数

36

被引用文献数

13 47

---

Increasing evidence from the fields of neurophysiology and neuropathology has uncovered the role of polyunsaturated fatty acids (PUFA) in protecting neuronal cells from oxidative damage, controlling inflammation, regulating neurogenesis, and preserving neuronal function. Numerous epidemiological studies have shown that deficits in the dietary PUFA docosahexaenoic acid and eicosapentaenoic acid are associated with the onset and progression of neuropsychiatric illnesses such as dementia, schizophrenia, depression, and posttraumatic stress disorder (PTSD). Recent clinical trials have offered compelling evidence that suggests that n-3 PUFA could reduce depressive, psychotic, and suicidal symptoms, as well as aggression. Although many studies have had the validity of their results questioned because of small sample size, several studies have indicated that n-3 PUFA are useful therapeutic tools for the treatment of dementia, major depression, bipolar disorder, and PTSD. These findings suggest that the pharmacological and nutritional actions of n-3 PUFA may be beneficial in certain neuropsychiatric illnesses. This review article outlines the role of PUFA in neurodevelopment and the regulatory mechanisms in neuronal stem cell differentiation and also the possible use of PUFA as a prescription medicine for the prophylaxis or treatment of neuropsychiatric illnesses such as dementia, mood disorder, and PTSD.

著者

Zhou Wu Hiroshi Nakanishi

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.126, no.1, pp.8-13, 2014-09-20 (Released:2014-09-20)

参考文献数

30

被引用文献数

9 62

---

Neuroinflammation, inflammation of the brain, is strongly implicated in Alzheimer’s disease (AD), which can be enhanced by systemic inflammation. Therefore, the initiation and progression of AD are affected by systemic diseases such as cardiovascular disease and diabetes. This concept suggests a possible link between periodontitis and AD because periodontitis is a peripheral, chronic infection that elicits a significant systemic inflammatory response. There is now growing clinical evidence that chronic periodontitis is closely linked to the initiation and progression of AD. Recent studies have suggested that leptomeningeal cells play an important role in transducing systemic inflammatory signals to the brain-resident microglia, which in turn initiate neuroinflammation. Furthermore, it is apparent that senescent-type microglia respond in an exaggerated manner to systemic inflammation. It is estimated that a high percentage of adults are suffering from periodontitis, and the prevalence of periodontitis increases with age. Therefore, chronic periodontitis can be a significant source of covert systemic inflammation within the general population. The present review article highlights our current understanding of the link between periodontitis and AD.

著者

Nian-Hong Chen Jian-Wen Liu Jian-Jiang Zhong

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.108, no.2, pp.212-216, 2008 (Released:2008-10-21)

参考文献数

15

被引用文献数

41 79

---

The effect of ganoderic acid Me (GA-Me), which was purified from the fermentation mycelia of the traditional Chinese medicinal mushroom Ganoderma lucidum as reported (Tang W, Gu TY, Zhong JJ. Biochem Eng J. 2006;32:205–210), on anti-invasion was investigated. Wound healing assay indicated that GA-Me inhibited cell migration of 95-D, a human highly metastatic lung tumor cell line, in dose- and time-dependent manners. Results of cell aggregation and adhesion assays showed that GA-Me promoted cell homotypic aggregation and inhibited cell adherence to extracellular matrix (ECM). In addition, GA-Me suppressed matrix metalloproteinases 2/9 (MMP2/9) gene expressions at both mRNA and protein levels in 95-D cells according to qRT-PCR and Western blotting, respectively. The results demonstrated that GA-Me effectively inhibited tumor invasion, and it might act as a new MMP2/9 inhibitor for anti-metastasis treatment of carcinoma cells.

著者

Kanako Miyano Yuka Sudo Akinobu Yokoyama Kazue Hisaoka-Nakashima Norimitsu Morioka Minoru Takebayashi Yoshihiro Nakata Yoshikazu Higami Yasuhito Uezono

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.14R13CP, (Released:2014-11-22)

参考文献数

30

被引用文献数

7 45

---

The G protein–coupled receptors (GPCRs) form the largest and the most versatile superfamily that share a seven-transmembrane-spanning architecture. GPCR-signaling is involved in vision, taste, olfaction, sympathetic/parasympathetic nervous functions, metabolism, and immune regulation, indicating that GPCRs are extremely important therapeutic targets for various diseases. Cellular dielectric spectroscopy (CDS) is a novel technology that employs a label-free, real-time and cell-based assay approach for the comprehensive pharmacological evaluation of cells that exogenously or endogenously express GPCRs. Among the biosensors that use CDS technology, the CellKeyTM system not only detects the activation of GPCRs but also distinguishes between signals through different subtypes of the Gα protein (Gs, Gi/o, and Gq). In this review, we discuss the traditional assays and then introduce the principles by which the CellKeyTM system evaluates GPCR activation, followed by a perspective on the advantages and future prospects of this system.