Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 397 records · Page 22Linked to original sources

PubMed1996

Inhibitory effect of phorbol 12,13-dibutyrate on norepinephrine-induced contraction in rabbit iris dilator muscle.

The hypothesis that the increase in Ca2+ sensitivity on norepinephrine-induced contraction of smooth muscles and also the decrease of the norepinephrine-induced sustained level of intracellular Ca2+ concentration are produced by the activation of protein kinase C was tested. Phorbol 12,13-dibutyrate (PDB; 10(-6) M) relaxed the norepinephrine-induced sustained contraction in a concentration-dependent manner. On pretreatment with PDB a transient contraction was produced by the application of norepinephrine, but the sustained contraction was significantly reduced. The sustained elevations of intracellular Ca2+ concentration ([Ca2+]i) and the contraction induced by norepinephrine in fura-2-loaded preparations were decreased by the application of PDB. These inhibitory effects were antagonized by potent protein kinase inhibitors, 2-(1-(3-dimethylaminopropyl)-indol-3-yl)-3-(-indol-3-yl)-maleimide (GF 109203X) (10 (-6) M) and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) (10 (-6) M), but were not affected by a protein kinase A/G inhibitor, N-(2-cinnamylaminoethyl)-5-isoquinolinesulfonamide (H-88) (10(-6) M). The slope of the regression line for norepinephrine for [Ca2+]i and tension was significantly steeper than those obtained with high K+. Also, on pretreatment with PDB the Ca2+ sensitivity of the K(+)-induced contraction was decreased, but the Ca2+ sensitivity of norepinephrine-induced contraction tended to be increased. These observations indicate that PDB induces a decrease of [Ca2+]i on Ca2+ mobility and an increase of Ca2+ sensitivity on contraction of smooth muscle through the activation of protein kinase C.

Adrenergic alpha-Agonists↗

PubMed1996

Galanin inhibits long-term potentiation at Schaffer collateral-CA1 synapses in guinea-pig hippocampal slices.

The role of galanin on long-term potentiation (LTP) of the field excitatory postsynaptic potentials (fEPSPs) at Schaffer collateral-CA1 synapses was investigated in guinea-pig hippocampal slices. Application of galanin (10(-7) M) inhibited the magnitude of LTP without any changes in the amplitude of fEPSP prior to tetanic stimulation. A putative central nervous system (CNS) type galanin receptor antagonist, galanin(1-13)-Pro-Pro-(Ala-Leu)2-Ala-Amide (M40), did not modify the magnitude of LTP when applied alone. However, M40 significantly reversed the inhibition by galanin when applied with galanin simultaneously. These findings suggest that galanin plays an inhibitory role through the CNS type galanin receptors.

Animals↗

PubMed1996

Distinctive immune response patterns of human and murine autoimmune sera to U1 small nuclear ribonucleoprotein C protein.

The Ul small nuclear ribonucleoprotein (snRNP), a complex of nine proteins with Ul RNA, is a frequent target of autoantibodies in human and murine systemic lupus erythematosus (SLE). Anti-Sm antibodies recognizing the B'/B, D, E, F, and G proteins of Ul snRNPs are highly specific for SLE, and are nearly always accompanied by anti-nRNP antibodies recognizing the Ul snRNP-specific 70K, A, and/or C proteins. Previous studies suggest that human anti-nRNP antibodies recognize primarily the U1-70K and Ul-A proteins, whereas recognition of Ul-C is less frequent. We report here that autoantibodies to U1-C are more common in human autoimmune sera than believed previously. Using a novel immunoprecipitation technique to detect autoantibodies to native Ul-C, 75/78 human sera with anti-nRNP/ Sm antibodies were anti-Ul-C (+). In striking contrast, only 1/65 anti-nRNP/Sm (+) MRL mouse sera of various Igh allotypes was positive. Two of ten anti-nRNP/Sm (+) sera from BALB/c mice with a lupus-like syndrome induced by pristane recognized Ul-C. Thus, lupus in MRL mice was characterized by a markedly lower frequency of anti-U1-C antibodies than seen in human SLE or pristane-induced lupus. The results may indicate different pathways of intermolecular-intrastructural diversification of autoantibody responses to the components of Ul snRNPs in human and murine lupus, possibly mediated by alterations in antigen processing induced by the autoantibodies themselves.

Animals↗

PubMed1996

Liver NK1.1+ CD4+ alpha beta T cells activated by IL-12 as a major effector in inhibition of experimental tumor metastasis.

We demonstrate herein evidence that IL-12-activated alpha beta T cells with intermediate TCR (NK1+ TCRint cells) in the liver inhibit metastases in the lung as well as in the liver metastases of i-v. injected tumors. IL-12 administration enhanced NK1 expression of NK1+ TCRint cells (NK1high) and increased CD4 weakly positive (CD4low) TCRint cells, while both CD4+ TCRint cells and double-negative TCRint cells were proportionally diminished. Accordingly, the major parts of NK1high TCRint cells are CD4low cells, and most of these cells are V beta 8+ cells. The cytotoxic assays of IL-12-stimulated hepatic mononuclear cells after treatment with respective Abs and complement in vitro and after sorting revealed that CD4low NK1high TCRint cells are cytotoxic effectors. When IL-12-stimulated hepatic mononuclear cells (but not splenocytes) were transferred into tumor-preinjected mice, EL-4 cell metastases in the liver as well as 3LL cell metastases in the lung were inhibited. The antimetastasis of hepatic mononuclear cells transfer was abrogated by the depletion of NK1+ cells, CD3+ cells, or CD4+ cells but not CD8+ cells before transfer. Moreover, transfer of these cells of nude mice into tumor-preinjected mice also inhibited metastases in both organs. Although NK1+ TCRint cells are nearly absent in the hepatic vein blood, a significant proportion of NK1high TCRint cells appeared by IL-12 administration. These results demonstrate that IL-12-stimulated liver NK1high TCRint cells, including extrathymic ones, are major effectors against tumor metastasis and suggest that the cells migrate and inhibit lung metastases.

Animals↗

PubMed1996

Inositol 1,4,5-trisphosphate-gated calcium transport through plasma membranes in nerve terminals.

We developed new biochemical approaches to demonstrate the presence of inositol 1,4,5-triphosphate (InsP3)-gated calcium channels in presynaptic plasma membranes (SPM) and their involvement in the presynaptic receptor-mediated Ca2+ influx into nerve terminals. In perfusion experiments using SPM vesicles preloaded with 45Ca2+, InsP3 elicited the release of 45CA2+ into perfusates in a saturable manner. The InsP3- evoked 45Ca2+ release from resealed SPM vesicles was more potent than that from resealed vesicles using any other subcellular fractions. Here we also report the involvement of InsP3-gated mechanisms in the presynaptic receptor-mediated Ca2+ influx into synaptosomes (nerve terminals) by use of such resealed vesicles reconstituted with purified Gi1.

Adenosine Triphosphate↗

PubMed1996

Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential.

Aberrant glycosylation expressed in specific types of human cancer may define stage, direction, and fate of tumor progression. Well-studied examples are expression of sialosyl-Lewis(x) or sialosyl-Lewis(a) in colorectal carcinoma and histo-blood group A and H/Le(y) in lung cancer. In renal cell carcinoma (RCC), expression of sialosyl-Lewis(x) has no correlation with metastatic potential. Clinicopathological studies have revealed that the degree of expression of disialosyl galactosylgloboside (DSGG) and monosialosyl galactosylgloboside is correlated with metastatic potential (to lung and lymph nodes) of RCC and inversely correlated with patient survival. In the present study, we compared the adhesion of RCC lines to sections of various tissues measured by Stamper-Woodruff assay and other similar assays under dynamic flow conditions. Of the eight RCC lines tested, only TOS-1 (which expresses DSGG) bound strongly to lung tissue sections. TOS-1 did not bind to sections of liver, kidney, or lymph nodes. In the same eight RCC lines, we also compared expression of DSGG and monosialosyl galactosylgloboside (reflected by reactivity with RM1 and RM2), overall ganglioside patterns, and correlation with lung tissue-binding ability. Under both static and dynamic flow conditions, the binding of TOS-1 cells to lung alveolar tissue was correlated with their DSGG expression, i.e., the binding was inhibited by RM2 but not by RM1. This binding was also inhibited by sialidase but not by EDTA (i.e., it was CA 2+ independent). The other seven cell lines (TOS-2, TOS-M, SMKT-R1, -R2, -R3, and -R4, and ACHN), which do not express DSGG, showed much weaker adhesion to lung tissue. None of the eight cell lines showed E- or P-selectin-dependent adhesion. These results suggest the existence of a yet-uncharacterized sialoadhesive receptor++ that specifically recognizes DSGG. This receptor could be the binding target in RCC metastasis to lung.

Carbohydrate Conformation↗

PubMed1996

Biphasic effects of intracerebroventricular interleukin-1 beta on mechanical nociception in the rat.

The effects of interleukin-1 beta on the mechanical nociceptive threshold in rat were examined using the paw-pressure test. An intracerebroventricular (i.c.v.) injection of interleukin-1 beta at doses of 10 and 100 pg/rat caused hyperalgesia to mechanical stimuli. Higher doses of interleukin-1 beta (1 and 10 ng/rat) induced an analgesic effect. The coadministration of the interleukin-1 receptor antagonist completely antagonized the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of alpha-helical-corticotropin-releasing factor [9-41] 15 min prior to interleukin-1 beta administration completely blocked the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of sodium salicylate 15 min prior to interleukin-1 beta administration inhibited the hyperalgesic effect of interleukin-1 beta, but not the analgesic effect. These results suggest that interleukin-1 beta produces biphasic effects on the mechanical nociceptive threshold through the interleukin-1 receptor in the brain and that a corticotropin-releasing factor-mediated pathway is involved. Furthermore, the hyperalgesic effect of interleukin-1 beta may be mediated by prostaglandins.

Animals↗

PubMed1996

LPS induces NK1.1+ alpha beta T cells with potent cytotoxicity in the liver of mice via production of IL-12 from Kupffer cells.

We recently reported that systemic administration of IL-12 into mice activates NK1.1+ alpha beta T cells with intermediate TCR (NK1+TCRint) and induces strong MHC-unrestricted cytotoxicity in C57BL/6 mice. In the present report, we examined the effect of LPS on Kupffer cells and NK1+TCRint, cells in C57BL/6 mice. Administration of LPS, as well as synthetic lipid A analogue (ONO-4007), but not detoxified LPS, induces the increase of NK1 expression of NK1+TCRint cells (NKlhighTCRint) and the acquisition of strong MHC-unrestricted cytotoxicity of these cells against NK-sensitive and NK-resistant targets as does IL-12 administration. LPS as well as ONO-4007 induced IL-12 mRNA in hepatic mononuclear cells, mainly in plastic-adherent Kupffer cells. LPS-induced cytotoxicity of hepatic mononuclear cells was greatly reduced by in vivo injections of anti-IL-12 Ab, to a lesser extent by anti-IFN-gamma Ab, but not by anti-IL-1 nor anti-TNF-alpha Ab. Pretreatment of mice with LPS induced inhibition of hepatic metastases of i.v. injected EL4 cells in C57BL/6 euthymic and athymic mice and this antimetastasis was inhibited by injection of anti-IL-12 Ab. This antimetastatic effect of LPS in the liver was also observed in different strains of mice and tumors, In contrast to IL-12, however, LPS was not so effective when administered after tumor inoculation. These results revealed that LPS (lipid A) stimulates NK1+TCRint cells through IL-12 production from Kupffer cells and suggest that bacterial components, probably including those from intestine, are activators of Kupffer cells and NK1+TCRint, cells in the liver. It is also suggested that the host condition as well as LPS-induced cytokines other than IL-12 may affect antitumor effect induced by LPS in the liver.

Animals↗

PubMed1996

Induction of interleukin-1 beta mRNA in the hypothalamus following subcutaneous injections of formalin into the rat hind paws.

The induction of interleukin-1 beta (IL-1 beta) mRNA in the rat brain following subcutaneous injection of formalin into the hind paws was investigated by in situ hydridization. IL-1 beta mRNA was markedly induced in the hypothalamus after the injection of formalin into both hind paws. On the other hand, IL-1 beta mRNA was scarcely observed in the hypothalamus of saline-injected control rats. The type of cells expressing IL-1 beta mRNA was likely glia because their nuclei were densely stained by Cresyl violet and were relatively small. The present results suggest that IL-1 beta mRNA is induced in the glial cells of the hypothalamus by persistent pain which is caused by formalin injection.

Animals↗

PubMed1996

Yearly variation of spontaneous somatic mutation frequency in the stamen hairs of Tradescantia clone KU 9 grown outdoors, which showed a significant increase after the Chernobyl accident.

Scoring of spontaneous somatic pink mutation frequency in the stamen hairs of Tradescantia clone KU 9, a heterozygote for flower color (blue/pink; the blue color being dominant), was carried out for 11 years on plants grown outdoors, during the period of May 11-31 (for 3 weeks) in every year from 1982 to 1992. Weekly and yearly variations of the spontaneous mutation frequency were observed, and such variations could mostly be correlated to the difference in temperature. That is, the mutation frequency was generally higher in the weeks and years when the temperature was relatively low, showing the strongest negative correlation with the average minimum temperature. The variations were also correlated to the diurnal temperature difference, the mutation frequency being higher with larger diurnal temperature difference in general. However, the mutation frequency observed in 1986 was exceptionally higher than that expected from the temperature for this year, and was very significantly higher than for other years. The scoring of mutation frequency was thus continued in 1986 for an additional 4 weeks (June 1-28), and it was confirmed that such higher mutation frequencies lasted for 6 weeks in total. The exceptionally high mutation frequency seemed to be related to the radioactive fallout which occurred in early to mid May of 1986, even in Japan, after the serious nuclear reactor accident at Chernobyl, and also to the biological concentrations of radioactive nuclides which subsequently occurred, although it was difficult to conclude this definitely. The mutation frequency in 1987 was second highest, and was also significantly higher than the lowest mutation frequency observed in 1990.

Climate↗

PubMed1996

Expression of cytokine genes and presence of enteroviral genomic RNA in endomyocardial biopsy tissues of myocarditis and dilated cardiomyopathy.

Viral infection, especially by enteroviruses, has been considered to be the most common cause of myocarditis, which may progress to dilated cardiomyopathy (DCM). Although the mechanism of progression remains uncertain, a cytokine-associated injury of myocytes has been proposed. Using reverse transcriptase polymerase chain reaction (RT-PCR), we examined the expression of interleukin 1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha) and the presence of enteroviral genomic RNA in endomyocardial biopsy tissues obtained from patients with myocarditis and DCM. We examined endomyocardial biopsy tissues obtained from 6 patients with myocarditis, 21 with DCM and 15 with non-infectious cardiac diseases as controls. In patients with myocarditis, endomyocardial biopsy was performed twice at an interval of 1 month to 8 years after the onset of myocarditis. We used RT-PCR to detect IL-1 beta, IL-6, IL-8 and TNF-alpha genes expression and nested RT-PCR (nRT-PCR) to detect enteroviral genomic RNA. IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in 100% (6/6) and enteroviral genomic RNA in 67% (4/6) of myocarditis patients at the first biopsy. At the second biopsy, IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in none, 50% (3/6), 67% (4/6) and 67% (4/6), respectively, and enteroviral genomic RNA in 67% (4/6). Four patients with myocarditis, in whom IL-8 and TNF-alpha genes and enteroviral genomic RNA were detected, progressed to DCM at the second biopsy. IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in none, 24% (5/21), 38% (8/21), 57% (12/21) of DCM patients, respectively. Enteroviral genomic RNA was detected in 43% (9/21) of DCM. Neither cytokine expression nor enteroviral genomic RNA were detected in the controls. the high incidence of cytokines, especially IL-6, IL-8 and TNF-alpha, expression in myocarditis and DCM, which might be induced by enteroviral infection, suggests that cytokines play an important role in myocytic damage leading to DCM.

Adult↗

PubMed1996

Features of autoantigens.

The major cellular antigens recognized by autoantibodies in SLE and other systemic autoimmune diseases have been identified and characterized over the past 25 years. The pioneering studies of Eng Tan demonstrate the importance of autoantibodies as diagnostic markers. However, why certain autoantibodies, such as anti-Sm, are pathognomonic of SLE, while others are markers of other autoimmune disease subsets, remains unanswered. This central question continues to drive much current research into the pathogenesis of SLE. Features of the autoantigens recognized by autoantibodies may provide important clues to the causes of lupus. Most autoantigens in systemic autoimmunity are multicomponent nucleoprotein complexes. These particles are encountered by the immune system as units, resulting in the tandem production of autoantibodies recognizing several components of the same complex. However, the intermolecular-intrastructural spreading of autoimmunity is regulated by mechanisms that at present are defined poorly. Also unexplained is the observation that the antigenic determinants recognized by autoantibodies are restricted and frequently correspond to active sites or functional domains. Analysis of experimental models of autoimmunity suggests that altering the structure of autoantigens, due to abnormal protein-protein interactions, hapten binding, altered degradation, or other mechanisms, could help to explain both the restricted patterns of autoantibody spreading and the selective targeting of antigenic sites. This may be a worthwhile area for further investigation of the pathogenesis of systemic autoimmune diseases.

Animals↗

PubMed1996

Estimation of the physical distance between major genomic markers in the Werner syndrome locus (8p11.2-12) by dual-color fish analysis.

The gene responsible for Werner syndrome (WS) is considered to be located between D8S131 and D8S87 in the 8p11.2-12 region that includes the closest marker D8S339 (Goto et al. (1992) Nature 355: 735-738). In this experiment, the order of major markers in this region was determined and the physical distances between them were estimated by dual-color fluorescence in situ hybridization (FISH) using P1, PAC and cosmid clone DNAs as probes. The fine overall order of telomere-D8S131-D8S339-GSR-PP2A beta-D8S283-D8S87-centromere was determined for the first time. The distance from D8S131 to D8S87 was estimated to be 1,634 kb. To our surprise, the distance between D8S131 and D8S87 is much shorter than previously estimated by recombination analysis, 8.3 cM equivalent to 8.3 Mb in physical distance. These information provide the basis for the positional cloning of WS gene and the identification of its mutation.

DNA↗

PubMed1996

Metallothionein content increased in the liver of mice exposed to magnetic fields.

Although recent studies have shown that various stress can induce metallothionein (MT) synthesis in animal tissues, the induction of MT synthesis by exposure to static magnetic fields (SMF) has not been reported. We measured MT levels in the liver, kidney and brain of mice exposed to SMF and also evaluated the effect of SMF exposure on the induction of hepatic MT by treatment with carbon tetrachloride (CCl4). The MT content in the liver was significantly increased by exposure to 4.7 T of SMF for 6, 24, or 48 h, whereas that in the kidney or brain was not changed compared to the control. The combination of CCl4 injection and SMF exposure induced elevation of the hepatic MT content exceeding that induced by either treatment alone. These results indicate that exposure to the strong SMF induces MT synthesis in the liver in mice and enhances the hepatic MT synthesis induced by CCl4 administration.

Animals↗

PubMed1996

Apoptotic process of cerebellar degeneration in experimental methylmercury intoxication of rats.

This report deals with the mechanism involved in the cerebellar degeneration following experimental methylmercury poisoning of male Wistar rats. The cerebellar granule cells of animals that exhibited typical hind leg paresis were shrunken and displayed marked nuclear pyknosis. At the ultrastructural level, the nuclei of these cells were condensed and fragmented, features which are characteristic of apoptosis. In situ staining for DNA strand breaks revealed that the pyknotic nuclei were positively labeled. DNA fragmentation was confirmed by agarose gel electrophoresis; a ladder pattern of multiples of approximately 200-base pair fragments, typical of apoptosis, was observed with the cerebellar DNA of the methylmercury-treated animals. These observations suggest that the degeneration of cerebellar granule cells by alkyl mercury compounds involves an apoptotic process.

Animals↗

PubMed1996

Effects of spontaneous myocardial oscillation on cardiac function: direct observation of the epicardial fluorescence image in calcium overloaded isolated hamster hearts.

OBJECTIVES: Calcium overload induces spontaneous cyclic calcium release from the sarcoplasmic reticulum, leading to spontaneous myocardial oscillation. This study was designed to elucidate (1) the effect of the myocardial oscillation on changes in ventricular performance and (2) how these changes relate to the strength of the diastolic spontaneous myocardial oscillation and the spatial extent--that is, in how extensive an area of the epicardium it occurred. METHODS: the isovolumic pressure of the left ventricle and epicardial fura 2 fluorescence in isolated hamster hearts were simultaneously observed at various calcium concentrations ([Ca2+]o). Endothelial cells and pericytes of the capillaries, preferentially stained by fura 2, were passively oscillated by surrounding myocytes during diastole at concentrations greater than 1 mmol/l of [Ca2+]o. The strength of the myocardial oscillation was evaluated as the root mean square (RMS) of fluctuation in the distance between endothelial cells or pericytes. The spatial extent of the myocardial oscillation was estimated as the appearance rate, defined as the ratio of the number of microscopic fields showing the capillary oscillation, to the total number of examined fields. RESULTS: Up to 4 mmol/l of [Ca2+]o, developed pressure and maximum rate of pressure rise significantly increased in a manner dependent on [Ca2+]o, but a further increase in [Ca2+]o significantly decreased these parameters. In the presence of ryanodine (2.5 mumol/l), developed pressure and maximum rate of pressure rise monotonously increased in a manner dependent on [Ca2+]o. Although the oscillation was never observed at 1 mmol/l of [Ca2+]o (appearance rate = 0%), it occurred in some of the microscopic fields at 2 and 4 mmol/l (appearance rate = 19.5 and 56.3%, respectively) and occurred in all microscopic fields at concentrations greater than 4 mmol/l (appearance rate = 100%). Ryanodine, which completely eliminated the capillary oscillation, inhibited the increase of both RMS and end-diastolic pressure by an increase in [Ca2+]o. CONCLUSIONS: Our data suggest that the myocardial oscillation impairs systolic and diastolic function in intact ventricle, and that these effects are associated with the spatial extent and the strength of the myocardial oscillation.

Animals↗

PubMed1996

Apoptosis of cultured microglia by the deprivation of macrophage colony-stimulating factor.

Promotion of microglial proliferation and differentiation by colony-stimulating factors (CSFs) and disappearances of microglia at the late neonatal stage by decreasing of CSFs have been reported. In this study, the effects of the deprivation of macrophage CSF (M-CSF) on enriched microglia in cultures were examined by cytochemical methods including in situ nick-end labeling for DNA fragmentation, and Carrazi's hematoxylin nuclear staining. When M-CSF was deprived from the culture medium: (1) at least 40% of the cells were weakly labeled by nick-end within 3 h and more than 70% of the cells were clearly labeled by 16 h; and (2) nuclear condensation or fragmentation, and formation of apoptotic bodies were observed within 48 h. LeY-positive immunoreactivity, identified as a characteristic of cells undergoing apoptosis, was observed on cells positively labeled by nick-end and condensed nucleus, and ones budding apoptotic bodies. From these results, it is conceivable that microglia undergo apoptosis when M-CSF is deprived from the culture medium and, therefore, require CSFs for their survival. This in vitro phenomenon suggests that one of the mechanisms of microglial disappearance in vivo after synaptogenesis may be due to apoptosis by decreasing level of CSFs.

Animals↗

PubMed1996

Dual effect of serotonin on formalin-induced nociception in the rat spinal cord.

To examine the role of the descending serotonergic system in the regulation of spinal nociceptive processing, the effects of serotonin (5-HT) and selective ligands for 5-HT receptor subtypes on persistent nociception were investigated. Formalin (5% formaldehyde) injected into the plantar region of the rat hindpaw induced two phases of aversive responses such as licking and biting. Intrathecal administration of selective 5-HT3 receptor antagonists, granisetron (0.1-100 pmol/rat) and ondansetron (1-1000 pmol/rat), reduced the second phase of the formalin-induced aversive responses without affecting the first one. The antinociceptive effect of granisetron (100 pmol/rat) was abolished when 5-HT was depleted from the lumbar cord by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT). In the 5,7-DHT-treated rats, intrathecal administration of 1-(m-chlorophenyl)-biguanide, a selective 5-HT3 receptor agonist, facilitated the aversive responses in the second phase whereas that of 8-OH-DPAT, a selective 5-HT1A receptor agonist, suppressed them. Intrathecal administration of 5-HT showed a dual effect on the second phase of the aversive responses in the 5,7-DHT-treated rats; 5-HT inhibited the aversive responses when administered at a low dose (0.1 nmol/rat) but facilitated them at a high dose (1 nmol/rat). In addition, the inhibitory and facilitatory effects of intrathecal 5-HT were blocked by its co-administration with NAN190, a 5-HT1A receptor antagonist, and granisetron, respectively. These results suggest that 5-HT suppresses formalin-induced nociception in the spinal cord via the 5-HT1A receptor and facilitates it via the 5-HT3 receptor.

5,7-Dihydroxytryptamine↗