Rapid deterioration of renal insufficiency after magnetic resonance imaging with gadolinium-based contrast agent.

Gadolinium (Gd)-based contrast media were introduced as alternatives to iodinated media for magnetic resonance imaging (MRI). Although originally thought to be non-nephrotoxic, Gd-based contrast media have recently been reported to be associated with acute kidney injury. The underlying mechanism of Gd-induced renal injury is not completely understood. We report an 80-year-old patient with buccal mucosa cancer for whom MRI with Gd-based contrast agent was conducted 3 times within 3 weeks. The patient developed rapid deterioration of preexisting renal insufficiency, and developed uremic symptoms and pulmonary edema. The patient was hemodialyzed 3 times. This resulted in improvement of renal function and clinical symptoms. This case emphasizes the potential nephrotoxicity of Gd-based contrast media and suggests that renal insufficiency, diabetes mellitus, old age and high dose of Gd-based contrast medium are risk factors for acute kidney injury.

Overexpression of inducible nitric oxide synthase and accumulation of 8-OHdG in nasopharyngeal carcinoma.

AIMS: Nitric oxide (NO), produced by inducible NO synthase (iNOS), has been suggested to cause oxidative stress, leading to 8-hydroxydeoxyguanosine (8-OHdG) accumulation and subsequent transversion mutation of DNA. The aim was to evaluate iNOS expression and the status of oxidative stress in nasopharyngeal carcinoma (NPC). METHODS AND RESULTS: Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein-Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed. Overexpression of iNOS, LMP-1 and EBER was observed in 62 (84.9%), 28 (38.4%) and 53 (72.6%) cases respectively. p53 gene mutation was found in 10 of 73 (13.7%) cases. Immunohistochemical iNOS expression was associated with the 8-OHdG labelling index, iNOS mRNA expression and p53 gene alteration (P < 0.0001, P = 0.016 and 0.0082 respectively). CONCLUSIONS: Our present findings suggest that the expression of iNOS induces oxidative stress in NPC. Although the presence of p53 mutation was associated with iNOS overexpression, the type of acid-base change of p53 was transition, but not transversion, which suggests that the p53 gene is not the direct target of DNA damage by 8-OHdG accumulation.

Congenital absence of the internal carotid artery diagnosed during investigation of trigeminal neuralgia.

Congenital absence of the unilateral internal carotid artery (ICA) was found in a patient during MR imaging examination for right trigeminal neuralgia. Magnetic resonance angiography showed complete absence of the right ICA and a large tortuous basilar artery (BA). The source images revealed a deformed right trigeminal nerve resulting from compression by the BA. Computed tomography of the skull base showed absence of the right carotid canal, suggesting agenesis of the right ICA. Longstanding hemodynamic stress may have caused the BA to become extremely tortuous, resulting in the trigeminal neuralgia.

Molecular and cellular characterization of a water-channel protein, AQP-h3, specifically expressed in the frog ventral skin.

Two cDNAs encoding frog aquaporin (AQP) were cloned from a cDNA library constructed for the ventral skin of the tree frog, Hyla japonica and sequenced. One AQP (Hyla AQP-h1) consisted of 271 amino-acid residues with high homology to toad AQP-t1, Rana CHIP28 (AQP1), and rat AQP1. The other AQP (AQP-h3) consisted of 271 amino-acid residues with higher homology to mammalian AQP2 than to mammalian AQP3. The predicted amino-acid sequence contained the conserved two NPA motifs found in all MIP family members and the putative six transmembrane domains. The sequence also confers mercurial sensitivity, which is common to all the AQPs except AQP0, AQP4 and AQP7. Potential N-glycosylation sites were present at Asn-44 in AQP-h1, and at Asn-124 and Asn-125 in AQP-h3. In addition, AQP-h3 had a putative phosphorylation site by protein kinase A at Ser-255, which is identical to mammalian AQP2. In swelling assays using Xenopus oocytes, AQP-h1 facilitates water permeability, whereas AQP-h3 displayed weak water permeability. Searching for the expression of these two AQP mRNAs revealed that AQP-h1 was expressed in most tissues, whereas AQP-h3 was observed only in the ventral skin. An antibody (ST-141) against the C-terminal peptide of the AQP-h3 protein recognized a 29.0 kDa-protein with a molecular mass close to that of the Hyla AQP-h3 protein and immunostained predominantly in the abdominal pelvic skin. In pelvic skin, the label for AQP-h3 was more intense in the upper layer of the stratum granulosum and was localized to both the apical and basolateral plasma membranes of the principal cells. These findings suggest that Hyla AQP-h3 plays a pivotal role in constitutively absorbing water from ventral pelvic skin.

SCCA1 expression in T-lymphocytes peripheral to cancer cells is associated with the elevation of serum SCC antigen in squamous cell carcinoma of the tongue.

Squamous cell carcinoma (SCC) antigen has been used for the management of SCC arising in various cites including head and neck region. However, the true mechanism of the elevation of this protein in the serum of patients with SCC is still unknown. SCC antigen belongs to the superfamily of serine protease inhibitors. Recently, molecular studies show that serum SCC antigen is transcribed by two nearly identical genes (SCCA1 and SCCA2), and is mainly produced by SCCA1. The objective of this study is to clarify the mechanism of the elevation of SCC antigen in oral tongue SCC patients and to identify cells histologically, which are responsible for serum SCC antigen production. In this study, we examined SCCA1 expression in a series of four head and neck SCC (HNSCC) cell lines, and found that all expressed equal to low SCCA1 protein as compared with the normal human oral keratinocyte. Using the double immunohistochemical technique to examine the expression pattern of SCCA1 in 86 cases of oral tongue squamous cell carcinoma, SCCA1 immunostaining was observed in the cytoplasm of cancer cells and T-lymphocytes peripheral to cancer cells. We also compared the clinicopathological features including serum SCC antigen level of the oral tongue SCC cases with the immunohistochemical SCCA1 expression pattern, and found that elevated serum SCC antigen level was significantly correlated with SCCA1 expression not in cancer cells, but in T-lymphocytes peripheral to cancer cells. These results suggest that T-lymphocytes peripheral to cancer cells may be responsible for serum SCC antigen production in HNSCC patients.

Maspin expression in stage I and II oral tongue squamous cell carcinoma.

BACKGROUND: A relatively high failure rate in the therapy of patients with early oral tongue squamous cell carcinomas (SCCs) is evidenced by untreated clinically negative neck lymph node metastasis. It is important to predict the malignant potential of oral tongue SCC in stage I and II patients, because the development of lymph node metastasis directly affects the prognosis of the patients. METHODS: We evaluated maspin expression immunohistochemically in patients with stage I and II oral tongue SCCs and determined whether the expression level may be a useful factor in predicting metastatic potential and prognosis of these SCCs. RESULTS: Clinical follow-up data showed a longer disease-free interval and overall survival periods for tumors immunohistochemically positive for maspin than for tumors negative for maspin, with the difference in disease-free interval being statistically significant (p =.01). The absence of maspin expression was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis (p =.03). CONCLUSIONS: Decreased maspin expression may be a significant factor associated with the metastatic potential of stage I and II oral tongue SCCs.

Bi-directional changes in affective state elicited by manipulation of medullary pain-modulatory circuitry.

The rostral ventromedial medulla contains three physiologically defined classes of pain-modulating neuron that project to the spinal and trigeminal dorsal horns. OFF cells contribute to anti-nociceptive processes, ON cells contribute to pro-nociceptive processes (i.e. hyperalgesia) and neutral cells tonically modulate spinal nociceptive responsiveness. In the setting of noxious peripheral input, the different cell classes in this region permit bi-directional modulation of pain perception (analgesia vs hyperalgesia). It is unclear, however, whether changes in the activity of these neurons are relevant to the behaving animal in the absence of a painful stimulus. Here, we pharmacologically manipulated neurons in the rostral ventromedial medulla and used the place-conditioning paradigm to assess changes in the affective state of the animal. Local microinjection of the alpha(1)-adrenoceptor agonist methoxamine (50.0 microg in 0.5 microl; to activate ON cells, primarily), combined with local microinjection of the kappa-opioid receptor agonist U69,593 (0.178 microg in 0.5 microl; to inhibit OFF cells), produced an increase in spinal nociceptive reactivity (i.e. hyperalgesia on the tail flick assay) and a negative affective state (as inferred from the production of conditioned place avoidance) in the conscious, freely moving rat. Additional microinjection experiments using various concentrations of methoxamine alone or U69, 593 alone revealed that the rostral ventromedial medulla is capable of eliciting a range of affective changes resulting in conditioned place avoidance, no place-conditioning effect or conditioned place preference (reflecting production of a positive affective state). Overall, however, there was no consistent relationship between place-conditioning effects and changes in spinal nociceptive reactivity. This is the first report of bi-directional changes in affective state (i.e. reward or aversion production) associated with pharmacological manipulation of a brain region traditionally associated with bi-directional pain modulation. We conclude that, in addition to its well-described pain-modulating effects, the rostral ventromedial medulla is capable of modifying animal behavior in the absence of a painful stimulus by bi-directionally influencing the animal's affective state.

A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin.

Orphanin FQ/nociceptin (OFQ/N) and its receptor share substantial structural features and cellular actions with classic opioid peptides and receptors, but have distinct pharmacological profiles and behavioral effects. Currently there is an active debate about whether OFQ/N produces hyperalgesia or analgesia. Using a well-defined brainstem pain-modulating circuit, we show that OFQ/N can cause either an apparent hyperalgesia by antagonizing mu opioid-induced analgesia or a net analgesic effect by reducing the hyperalgesia during opioid abstinence. It presumably produces these two opposite actions by inhibiting two distinct groups of neurons whose activation mediates the two effects of opioid administration. OFQ/N antagonism of the hyperalgesia may have significance for the treatment of opioid withdrawal and sensitized pain.

Evaluation of Epstein-Barr virus infection in sinonasal small round cell tumors.

Sinonasal undifferentiated carcinoma, olfactory neuroblastoma and malignant melanoma of the sinonasal regions are included within the category of small round cell tumors of the sinonasal region. It is difficult to diagnose these tumors on the basis of light-microscopic features alone, but, in some instances, immunohistochemical staining evaluating cytokeratin and S-100 protein, for example, is of value. On the other hand, the sinonasal region is a significant site for Epstein-Barr-virus (EBV)-related tumors, including sinonasal undifferentiated carcinoma or malignant lymphoma. Twenty-three sinonasal small round cell tumors (SSRCT) comprising 5 sinonasal undifferentiated carcinomas, 9 olfactory neuroblastomas and 9 malignant melanomas were evaluated for the presence of EBV infection by in situ hybridization for EBV-encoded RNA, combined with immunostaining for EBV-related proteins (LMP-1 and EBNA2). Furthermore, 55 SSRCT comprising 37 sinonasal undifferentiated carcinomas, 9 olfactory neuroblastomas, and 9 malignant melanomas were examined for the presence of cytokeratins (AE1/ AE3 and CAM5.2), S-100 protein and p53 protein using immunohistochemical staining. According to in situ hybridization for detecting EBV-encoded RNA 1 (EBER1), all of the sinonasal undifferentiated carcinomas showed clear, intense hybridization signals localized over the nuclei of the tumor cells and, in 3 out of 9 (33.3%) malignant melanomas, hybridization signals were also recognized. However, none of the olfactory neuroblastomas revealed hybridization signals. Immunohistochemically, 4 out of 5 (80%) sinonasal undifferentiated carcinomas were positive for LMP-1, whereas only 2 out 9 (22.2%) malignant melanomas and no olfactory neuroblastomas were positive. With regard to EBNA2, sinonasal undifferentiated carcinomas, malignant melanomas and olfactory neuroblastomas were all negative. Out of 37 sinonasal undifferentiated carcinomas 35 (94.6%) showed a diffuse positive immunoreaction for AE1/AE3, whereas neither olfactory neuroblastoma nor malignant melanoma revealed a positive reaction. All 9 malignant melanomas and 6 out of 9 olfactory neuroblastomas (75%) were positive for S-100 protein, whereas only 6 cases of sinonasal undifferentiated carcinomas (19.4%) were positive. As for p53 protein, 16 of 37 sinonasal undifferentiated carcinomas (43.2%) were positive, whereas neither olfactory neuroblastoma nor malignant melanoma revealed any positive reaction. The above results suggest that EBV infection is closely associated with sinonasal undifferentiated carcinomas, and that some malignant melanomas may also have a relationship with its infection. For the differential diagnosis of SSRCT, it is important to evaluate EBV infection along with immunohistochemical staining for cytokeratins and S-100 protein. The overexpression of p53 protein was found to be related to the oncogenesis of sinonasal undifferentiated carcinoma; however, there was no association between its overexpression and malignant melanoma or olfactory neuroblastoma.

Highly delta selective antagonists in the RVM attenuate the antinociceptive effect of PAG DAMGO.

The present study tested the hypothesis that endogenous opioid peptides acting at the delta-opioid receptor (DOR) in the rostral ventromedial medulla (RVM) contribute to the antinociception elicited by the mu-opioid receptor (MOR) agonist DAMGO in the midbrain periaqueductal gray (PAG). Following microinjection of DAMGO into the PAG, either the highly selective DOR antagonist TIPP[psi] or the DOR2 antagonist naltriben (NTB) was microinjected into the RVM. Both TIPP[psi] (1.0 microg) and NTB (5.0 ng) significantly attenuated the analgesic effect of PAG DAMGO but had no effect when given before PAG saline. These results confirm and extend previous studies suggesting that PAG mu-opioids activate a descending system with a DOR mediated endogenous opioid link in the RVM.

[Clinical analysis of parotid cancer].

A clinical study was performed on 42 patients with parotid cancers initially treated in our hospital from 1972 to 1997. The five-year cumulative survival rate was 69% in the whole group and 72% in the radical surgical treatment group (n = 40). The five-year survival rates according to stage were as follows: stage I, 95% (21); stage II, 75% (4); stage III, 0% (1); and stage IV, 37% (16). The factors influencing prognosis were cases of T3 and T4 (p < 0.05), stage III and IV (p < 0.01), and cervical lymph node metastasis (p < 0.01). Regarding treatment modalities, a partial parotidectomy appeared to be a curable surgical procedure for T1 cases. However, a lobectomy is recommended for T2 cases. Furthermore our study proposed that prophylactic supraomohyoid neck dissection should be necessary for mucoepidermoid carcinoma (high-grade malignancy) and undifferentiated carcinoma of T4N0 cases.

A progression to dermatofibrosarcoma protuberans with a fibrosarcomatous component: a special reference to the chromosomal aberrations.

Dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous areas (DFSP-FS) is differentiated from ordinary DFSP by its unfavourable prognosis. We carried out sequential analysis of numerical chromosomal abnormalities in two cases of DFSP during their progression to metastatic disease with FS areas (DFSP-M-FS). They were compared with nine cases of ordinary DFSP and three cases of DFSP-FS, but without metastases. Numerical chromosomal changes were examined by fluorescence in situ hybridization (FISH) using alpha-satellite centromeric probes for chromosomes 1, 8, 11 and 17. Numerical imbalances of chromosome 1 were not clarified. A gain of chromosome 8 was demonstrated in the two cases of DFSP-M-FS. A gain of chromosome 11 was observed in one of the two cases of DFSP-M-FS and in one case of DFSP-FS. A gain of chromosome 17 was demonstrated in both metastatic tumours and in recurrent tumours in two cases of DFSP-M-FS, in addition to two cases of DFSP-FS and four cases of ordinary DFSP with recurrent tumours or large tumours. This study raised the hypothesis that a gain of chromosome 17 developed in recurrent or large-sized DFSP, which occurs in high-risk groups with the possibility of a progression to FS.

Expression of bcl-2-, p53, and Ki-67 and outcome of patients with primary nasopharyngeal carcinomas following DNA-damaging treatment.

BACKGROUND: Recent studies suggest that apoptosis is important in the cell death induced by treatment that damages deoxyribonucleic acid (DNA). We assessed the correlation between the expression of the apoptosis-related proteins, p53 and bcl-2, and the clinical outcome of patients with nasopharyngeal carcinomas (NPCs) who were treated with both DNA-damaging treatments. We also assessed the level of Ki-67, a marker of cell proliferation, in these tumors. METHODS: We evaluated statistically the relationships among the expression of p53, bcl-2, and Ki-67 and clinicopathologic factors, the sensitivity to radiation, the incidence of distant metastases, and survival. RESULTS: The group that was positive for p53 tended to be resistant to radiotherapy and to have a significantly poorer prognosis (p = .05). CONCLUSIONS: The enhanced expression of p53 may be a prognostic factor in patients with NPCs whose tumor is resistant to therapy that damages DNA.

A novel histamine 2(H2) receptor antagonist with gastroprotective activity. I. Synthesis and pharmacological evaluation of N-phenoxypropylacetamide derivatives with thioether function.

In an attempt to develop new types of anti-ulcer agents, a series of N-(phenoxypropyl)acetamide derivatives with a thioether moiety and their sulfur-oxidized analogues were synthesized and evaluated for histamine H2-receptor antagonistic activity, Ca antagonistic activity and gastric anti-secretory activity in the lumen-perfuseed rat. Selected compounds were also tested for gastroprotective activity, which was expected to be based on Ca antagonistic activity. Structure-activity relationships are discussed. As a thioether moiety, -CH2-S(O)p-CH2-Ar (Ar; phenyl or furyl) was found to be optimal for the above activities. Especially, N-[3-[(3-(piperidinomethyl) phenoxy]propyl]acetamide with a benzyl sulfinyl, benzylsulfonyl, furfurylsulfinyl or furfurylsulfonyl group showed potent gastroprotective activity upon oral administration in a rat model. These compounds are candidates for novel anti-ulcer drugs with gastric anti-secretory and gastroprotective activities. 2-Furfurylsulfinyl-N-[3-[(piperidinomethyl)phenoxy]propyl]ac etamide was the most potent among the compounds tested and was given the code designation FRG-8701.

A novel histamine 2(H2) receptor antagonist with gastroprotective activity. II. Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings.

We recently found that N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide derivatives with a thioether function showed gastric anti-secretory and gastroprotective activities and that the thioether function (particularly furfurylthio or furfurylsulfinyl) was essential for gastroprotection. In the present study, a series of 2-furfurylthio and 2-furfurylsulfinyl acetamide derivatives were synthesized and evaluated for histamine H2 receptor antagonistic activity, gastric anti-secretory activity and gastroprotective action. Based on the structure of N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide, we designed compounds, in which the 3-(piperidinomethyl)phenoxy part is substituted with many types of heteroaromatic ring attached to the tertiary amine and the propyl group is replaced with other carbon linkages. Structure-activity relationships are discussed. 2-Furfurylsulfinyl-N-[4-[4-(piperidinomethyl)-2-pyridylox y]- (Z)-2-butenyl]acetamide was the most potent among the tested compounds and was given the code designation FRG-8813.

[Circadian rhythm of parasympathetic nervous function in asthmatic children].

We examined the circadian rhythm of parasympathetic nervous function in asthmatic children. The subjects were 80 patients with asthma (mild 54 patients, moderate 15 patients and severe 11 patients) and 90 individuals in healthy children. All the patients underwent 24-electrocardiography in normal condition. We measured the %RR50 for hour and analyzed the rhythm using the single cosine fitting method, comparing the values of the Amplitude, the MESOR and the Acrophase in terms of the therapy and also the severity of asthma. Circadian rhythm disappeared in 9 of the 80 asthmatic children and was observed in all the individuals in the healthy children. The value of MESOR was lower in the asthmatic children than in the healthy children. There was no significant difference between the different severity or therapies in each group. In some asthmatic children, the circadian rhythm of parasympathetic nervous function disappeared, the parasympathetic nervous function was low in remission. It is suggested that the disorder of biologic rhythm is related to the pathogenesis of asthma.

Overexpression of bcl-2 protein in synovial sarcoma: a comparative study of other soft tissue spindle cell sarcomas and an additional analysis by fluorescence in situ hybridization.

The expression of bcl-2 protein was analyzed in 19 synovial sarcomas and 29 additional soft tissue spindle cell sarcomas as controls by the immunohistologic staining of paraffin-embedded specimens; 15 of 19 (79%) synovial sarcoma cases were positive, but all other spindle cell sarcomas were negative including 20 leiomyosarcomas, 4 malignant peripheral nerve sheath tumors, and 4 fibrosarcomas. In 4 cases of bcl-2-positive synovial sarcoma (3 biphasic and 1 focally glandular type), bcl-2 protein staining was much stronger in the spindle cells than in the epithelial cells. A fluorescence in situ hybridization (FISH) analysis with centromeric and whole chromosome painting probes for chromosome 18 and X was performed on 7 synovial sarcomas. The six cases of bcl-2-positive synovial sarcoma consisted of five cases with the t(X; 18) and one case with tetrasomy of chromosome 18 and X. It has been speculated that bcl-2 protein expression is caused by the 14; 18 translocation and other abnormalities of chromosome 18. This study thus showed the feasibility of such a correlation between bcl-2 protein expression and the characteristic cytogenetic abnormality in the synovial sarcoma-X; 18 translocation. In addition, bcl-2 protein also appears to be a characteristic marker of synovial sarcoma and is thus considered to be potentially useful in distinguishing synovial sarcoma from other spindle cell sarcomas.

Cyclin D1 overexpression in primary hypopharyngeal carcinomas.

BACKGROUND: Hypopharyngeal squamous cell carcinomas (HPCS) are associated with an extremely poor prognosis. Generally, conventional clinicopathologic factors have only limited value as prognostic factors for this malignancy. It is therefore clinically important to identify new prognostic factors that accurately reflect the biologic aggressiveness of this malignancy. The amplification and overexpression of the cyclin D1 protooncogene have been reported in a variety of malignancies, and are thought to be related to tumor progression. Based on this phenomenon, the authors immunohistochemically evaluated overexpression of the cyclin D1 gene in 42 cases of primary HPCS. In addition, the immunohistochemical staining of the proliferation marker MIB-1 (Ki-67 antibody) was also performed. METHODS: Formalin fixed, paraffin embedded biopsy specimens obtained prior to treatment were examined. Cyclin D1 and Ki-67 were detected using monoclonal antibodies by means of the streptavidin-biotin method. The relationship between cyclin D1 overexpression and the stage, histologic grade, presence of lymph node metastases, proliferation index, and survival was then statistically analyzed. The correlation between the proliferation index, other clinicopathologic factors, and survival was also evaluated. RESULTS: Twenty-three (54.8%) HPCS specimens showed a 20% or greater immunoreactivity for cyclin D1. Cyclin D1 overexpression was related to cervical lymph node metastases (P = 0.037) but not to clinical stage, histologic grade, or the proliferation index. Cyclin D1 negative tumors were associated with a significantly better prognosis (P = 0.023), particularly in patients who underwent multimodality treatment. Finally, the MIB-1 labeling index showed no correlation with either the clinicopathologic parameters or overall survival. CONCLUSIONS: Based on these findings, cyclin D1 immunohistochemical staining is considered to be useful, not only as a prognostic factor for HPCS, but also as a means of determining the optimum treatment for each individual patient. Conversely, the MIB-1 labeling index appears to have no clinical significance in HPCS.

The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development.

We previously reported that a variant with extra amino acid residues exists in the metabotropic glutamate receptor subtype 5 (mGluR5). Either of the two isoforms, named mGluR5b and mGluR5a for the isoforms with and without the inserted sequence, respectively, generated Ca(2+)-activated Cl- current when expressed in Xenopus oocytes. We herein report that these two isoforms are produced by the alternative splicing of the exon skipping type. When examined during the course of postnatal development, the major mGluR5 isotype mRNA was observed to switch from mGluR5a to mGluR5b in the rat hippocampus and the cerebral cortex. We also investigated two cell lines that could be differentiated into neuron-like cells in vitro. Whereas the mGluR5b mRNA was hardly detectable in either undifferentiated or differentiated NG108-15 cells, the relative amounts of the two variant mRNAs changed after the induction of differentiation in the P19 cells. An extracellular application of trans-D,L-1-amino-1,3-cyclopentanedicarboxylate on the neuron-like P19 cells induced intracellular Ca2+ mobilization, thus suggesting that the cells could express functional mGluR(s) coupled to phospholipase C and other components that could mediate the signal transduction pathway. This cell line may thus provide a model system for studying both mGluR5 expression and other mGluR-induced phenomena at the molecular level.