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T Katafuchi

Publications and source records attributed to T Katafuchi.

At least 19 recordsLinked to original sources

Action of neuropeptide Y on nociceptive transmission in substantia gelatinosa of the adult rat spinal dorsal horn.

Effects of neuropeptide Y (NPY) on substantia gelatinosa neurons were investigated in adult rat spinal cord slices using blind whole-cell patch-clamp technique. Bath application of NPY (1 microM) induced a membrane hyperpolarization, resulting in a suppression of the dorsal root stimulation-induced action potentials in 24% of the substantia gelatinosa neurons tested. In voltage clamp mode, NPY produced an outward current dose-dependently in about one third of substantia gelatinosa neurons at the holding potential of -60 mV, which was not affected by tetrodotoxin (1 microM). The NPY-induced current was suppressed by perfusion with a Ba2+-containing external solution and a Cs2SO4 or tetraethylammonium-containing pipette solution. In addition, The NPY-induced outward currents reversed its polarity near the equilibrium potential of K+ ions (-93 mV). The response to NPY recorded with guanosine-5'-O-(2-thiodiphosphate)-beta-S (GDP-beta-S) containing pipette solution was abolished 30 min after patch formation, suggesting that the response was mediated by the G-protein-coupled receptors. Application of an NPY-Y1 selective agonist, [Leu(31), Pro(-34)]-NPY (1 microM), for 30 s also induced an outward current with a similar time course and amplitude to that induced by NPY. On the other hand, the NPY response was blocked by a simultaneous application of NPY-Y1 selective antagonist, BIBP 3226 (1 microM). No significant changes were found in amplitude and frequency of miniature excitatory postsynaptic currents and dorsal root evoked excitatory postsynaptic currents by NPY. In addition, NPY did not affect both of the miniature inhibitory postsynaptic currents and evoked inhibitory postsynaptic currents, mediated by either the GABA or glycine receptor. These findings, taken together, suggest that NPY produces an outward current in substantia gelatinosa neurons through G-protein coupled, and NPY-Y1 receptor-mediated activation of K+ channels without affecting presynaptic components. The inhibition of the synaptic transmission from the primary fibers to the substantia gelatinosa neurons is considered to contribute to the antinociceptive effects of NPY.

Animals↗

Analysis of receptive fields revealed by in vivo patch-clamp recordings from dorsal horn neurons and in situ intracellular recordings from dorsal root ganglion neurons.

It has been thought that spinal dorsal horn neurons receive convergent inputs from not only somatosensory but also visceral pathways. For instance, the referred pain is presumed to be due to the convergence of sensory inputs from cardiac and shoulder receptive fields. However, precise investigation has not been made from dorsal horn neurons yet, because of difficulty in studying the pathways from those regions by means of conventional electrophysiology. The purpose of this study is to clarify the convergent inputs to single dorsal horn neurons from wide receptive fields using an in vivo patch-clamp recording technique from the superficial spinal dorsal horn and an intracellular recording from dorsal root ganglion neurons that keep physiological connections with the peripheral sites. Identified dorsal root ganglion neurons received an input from a quite small area, about 1 x 1 mm in width of the skin. In contrast, substantia gelatinosa neurons in the spinal cord received inputs from an unexpectedly wide area of the skin. Previous extracellular recordings have, however, revealed that substantia gelatinosa neurons have small receptive field. This discrepancy is probably due mainly to an availability of the in vivo patch-clamp method to analyze sub-threshold synaptic responses. In contrast, the extracellular recording technique allows us to analyze predominantly the firing frequency of neurons. Thus, the in vivo patch-clamp recordings from dorsal horn neurons and the intracellular recordings from DRG neurons will be useful for well understanding the sensory processing in the spinal cord.

Animals↗

Functional reorganization of the spinal pain pathways in developmental and pathological conditions.

Following inflammation, a subpopulation of Abeta afferents that terminates preferentially in deeper laminae have been shown to extend their axons to the superficial dorsal horn, particularly substantia gelatinosa (SG). Similarly, SG neurons in immature spinal cord receive mainly Abeta afferent inputs. To clarify whether the reorganized sensory pathway in the inflamed rats has a functional similarity with that in the developmental state, we compared synaptic inputs from primary afferents using in vitro and in vivo patch-damp recordings from SG neurons. SG neurons in the mature state had monosynaptic inputs from Adelta and C afferents, while only a few neurons received inputs from Abeta afferents. Following inflammation, the Abeta afferents extended their axons to SG and established functional monosynaptic transmission. Meanwhile, SG neurons in the immature state received preferentially Abeta as well as Adelta afferent inputs, and the majority of Abeta afferent inputs were monosynaptic. These observations support the idea that the sprouting of the large afferent fibres observed in inflamed rats is, at least in part, a regeneration process. However, the process, maybe distinct at some point from the process during development, therefore, produces pathological pain. Though the idea that the regeneration mimics the developmental process has been widely accepted, other possibilities cannot be excluded.

Afferent Pathways↗

Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running wheel activity and brain interferon-alpha mRNA in rats: a model for immunologically induced fatigue.

Following 2 weeks acclimation to the running wheel in the home cages, an i.p. injection of a synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly I:C, 3 mg/kg), was performed to produce the immunologically induced fatigue in rats. The daily amounts of spontaneous running wheel activity decreased to about 40-60% of the preinjection level until day 9 with normal circadian rhythm, then gradually returned to the baseline level by day 14. Rats given a heat exposure (36 degrees C for 1 h) for the consecutive 3 days showed an increase in activity except for the first day. In the open field test, the total moving distance and the number of rearing of the poly I:C-injected rats decreased on day 1, but they were not different from the saline-injected group on day 7, suggesting that the poly I:C-induced fatigue on day 7 was not due to the peripheral problems such as muscle/joint pain, but involved the CNS. Quantitative analysis of mRNA levels using a real-time capillary reverse transcriptase-polymerase chain reaction (RT-PCR) method revealed that interferon-alpha (IFN-alpha) mRNA contents in the cortex, hippocampus, hypothalamic medial preoptic, paraventricular, and ventromedial nuclei were higher in the poly I:C group than those in the saline and heat-exposed groups on day 7, although the amount of interleukin-1 beta mRNA showed no differences. Serum adrenocorticotropic hormone and catecholamine levels were not significantly different between groups. The present results indicate that the prolonged fatigue induced by poly I:C, which is evaluated by the spontaneous running wheel activity, can be used as an animal model for the immunologically induced fatigue associated with viral infection, and suggest that brain IFN-alpha may play a role in this model.

Adrenocorticotropic Hormone↗

Cardiac fibroblasts are major production and target cells of adrenomedullin in the heart in vitro.

OBJECTIVE: Adrenomedullin (AM) is a potent vasodilator peptide. Plasma AM concentration is increased in patients with various heart diseases, and both myocytes (MCs) and non-myocytes (NMCs) secrete AM and express its receptors. These facts suggest that cardiac cells possess an autocrine/paracrine capability mediated by AM. METHODS: MCs and NMCs were prepared from cardiac ventricles of neonatal rats. AM and endothelin-1 concentrations were measured by radioimmunoassays, and interleukin-6 level by a specific bioassay. Total nitrite/nitrate contents were measured with a fluorescence assay kit. RESULTS: A basal secretion rate of AM from NMCs was 2.8-fold higher than that from MCs. Interleukin-1beta, tumor necrosis factor-alpha and lipopolysaccharide stimulated AM secretion from NMCs but not from MCs. AM stimulated interleukin-6 production in the presence of these cytokines or lipopolysaccharide, which was more prominent in NMCs. In the presence of interleukin-1beta, AM augmented nitric oxide synthesis 2.7-fold in NMCs, but slightly in MCs. NMCs secreted endothelin-1 at a rate nine times higher than MCs, and AM inhibited endothelin-1 secretion from NMCs. CONCLUSION: This in vitro study suggests that AM in the heart is mainly produced in NMCs and exerts its effects through NMCs, especially under inflammatory conditions.

Adrenomedullin↗

Regulation of adrenomedullin secretion from cultured cells.

Characterization of immunoreactive adrenomedullin (AM) secreted from cultured human vascular smooth muscle cells and 7 other cells indicates that AM is synthesized and secreted from all cultured cells we surveyed. The secretion rate of AM measured ranges from 0.001-6.83 fmol/10(5) cells/h, and endothelial cells, vascular smooth muscle cells and fibroblasts generally secrete AM at high rates. Based on the results of regulation of AM secretion from vascular wall cells, fibroblasts, macrophages and other cells measured in this and previous studies, AM secretion is found to be generally stimulated by inflammatory cytokines, lipopolysaccharide (LPS) and hormones. Especially, vascular smooth muscle cells and fibroblasts elicited uniform and strong stimulatory responses of AM secretion to tumor necrosis factor (TNF), interleukin-1 (IL-1), LPS and glucocorticoid, but endothelial cells did not elicit such prominent responses. AM secretion of monocyte-macrophage was mainly regulated by the degree of differentiation into macrophage and activation by LPS and inflammatory cytokines including interferon-gamma. The other examined cells showed weaker responses to LPS and IL-1. Although cultured cells may have been transformed as compared with those in the tissue, these data indicate that AM is widely synthesized and secreted from most of the cells in the body and functions as a local factor regulating inflammation and related reactions in addition to as a potent vasodilator. The responses of AM secretion to LPS and inflammatory cytokines suggest that fibroblasts, vascular smooth muscle cells and macrophage are the major sources of AM in the septic shock.

Adrenomedullin↗

Enhanced expression and release of C-type natriuretic peptide in freshwater eels.

C-type natriuretic peptide (CNP) is recognized as a paracrine factor acting locally in the brain and periphery. To assess the role of CNP in teleost fish, a cDNA encoding a CNP precursor was initially cloned from the eel brain. CNP message subsequently detected by ribonuclease protection assay, using the cDNA as probe, was most abundant in the brain followed by liver, gut, gills, and heart. Expression was generally higher in freshwater (FW) than in seawater (SW) eels, but not in the brain. Plasma CNP concentration measured by a newly developed homologous radioimmunoassay for eel CNP was higher in FW than in SW eels. The CNP concentration was also higher in the heart of FW eels but not in the brain. These results show that CNP is abundantly synthesized in peripheral tissues of FW eels and secreted constitutively into the circulation. Therefore, CNP is a circulating hormone as well as a paracrine factor in eels. Together with our previous demonstration that CNP-specific receptor expression is enhanced in FW eels, it appears that CNP is a hormone important for FW adaptation. Because atrial NP (ANP) promotes SW adaptation in eels, CNP and ANP, despite high sequence identity, appear to have opposite effects on environmental adaptation of the euryhaline fish.

Amino Acid Sequence↗

Comparable effects of adrenalectomy and C fiber depletion on delayed-type hypersensitivity in rats.

OBJECTIVE: To determine the influence of the hypothalamic-pituitary-adrenal (HPA) axis and sensory C fibers on cell-mediated immunity, the time course of allergic contact dermatitis (ACD) was examined in normal, adrenalectomized (ADX) and capsaicin (CAP)-treated rats. METHODS: Five days after sensitization with 2,4-dinitro-1-fluorobenzene (DNFB) onto the back, rats were challenged with DNFB on the pinna. ADX or CAP treatment was performed a week before the sensitization. RESULTS: Ear swelling in normal rats reached a peak 24 h after the challenge and subsided gradually to about half of this peak 72 h afterwards. Plasma ACTH levels increased about 9 times more than those of nonsensitized rats 72 h after the challenge. ADX rats, in which the plasma corticosterone level was significantly lower than that in sham-operated animals, exhibited more rapid development of ACD, which reached a peak 12 h after the challenge. However, the swelling returned to about half of the maximum within 48 h. In CAP-treated rats, ACD reached a peak 6 h after the challenge and recovered quickly as in ADX rats. Plasma ACTH levels in CAP- treated rats were significantly lower than those in vehicle-treated rats. CONCLUSIONS: The rapid development of and recovery from ACD in ADX and CAP-treated rats, both of which showed suppression of the HPA axis, indicated a biphasic action of the HPA axis on ACD, i.e. inhibitory in the early phase but augmentative in the late phase of ACD.

Adrenalectomy↗

Brain fluorine-18 fluorodeoxyglucose imaging with dual-head coincidence gamma camera: comparison with dedicated ring-detector positron emission tomography.

BACKGROUND AND PURPOSE: Dual-head coincidence gamma camera (DHC) imaging has been proposed as an alternative to dedicated ring-detector positron emission tomography (dr-PET) for clinical fluorodeoxyglucose (FDG) studies. The purpose of this investigation was to assess the quality of DHC images in FDG studies of the human brain. METHODS: Seven healthy volunteers and 12 patients with various cerebral disorders underwent consecutive brain dr-PET and DHC with FDG. All sets of images were compared semiquantitatively using regions of interest. RESULTS: Cortical count ratios to the cerebellum on DHC and dr-PET images did not differ significantly among the volunteers, except in the superior frontal cortex and thalamus. In all studies including those of cerebral disorders, the mean cortical-to-cerebellar ratios of DHC and dr-PET images correlated closely. CONCLUSION: FDG imaging with DHC delineated the metabolic distribution of glucose in the brain as well as dr-PET did, except in the superior frontal cortex and thalamus. Therefore, DHC may be a dedicated cost-effective means of detecting metabolic abnormalities in the brain.

Adult↗

Estimation of myocardial perfusion and viability using simultaneous 99mTc-tetrofosmin--FDG collimated SPECT.

UNLABELLED: This study was designed to elucidate the usefulness of crosstalk correction for dual-isotope simultaneous acquisition (DISA) with 99mTc-tetrofosmin and FDG in estimating myocardial perfusion and viability. METHODS: Eighteen patients with coronary artery disease were studied. First, SPECT was performed with a low-energy high-resolution collimator after a single injection of 99mTc-tetrofosmin (single 99mTc-tetrofosmin). Second, PET and DISA with an ultra-high-energy collimator were performed after glucose loading and an injection of FDG. DISA was designed to operate with simultaneous 3-channel acquisition, and weighted scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak was performed by modification of an existing dual-window technique. The FDG SPECT images were compared with the images obtained by PET. Both crosstalk-corrected and uncorrected 99mTc-tetrofosmin images were generated and compared with the single 99mTc-tetrofosmin images. RESULTS: Regional percentage uptake of FDG agreed well between DISA and PET. However, regional percentage uptake of 99mTc-tetrofosmin was generally higher on the uncorrected 99mTc-tetrofosmin images than on the single 99mTc-tetrofosmin images, especially in areas of low flow (percentage count of 99mTc-tetrofosmin > or = 50%). The crosstalk correction contributed to improving the agreement between regional percentage uptakes and significantly improved the detectability of myocardial perfusion-metabolism mismatching. CONCLUSION: With 3-channel acquisition and weighted-scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak, DISA with 99mTc-tetrofosmin and FDG is feasible for assessing regional myocardial perfusion and viability.

Aged↗

Adrenomedullin suppresses interleukin-1beta-induced tumor necrosis factor-alpha production in Swiss 3T3 cells.

We demonstrated that adrenomedullin (AM) inhibited interleukin-1beta-induced tumor necrosis factor-alpha (TNF-alpha) secretion and gene transcription in Swiss 3T3 fibroblasts maximally to 23% and 18% of control, while the other peptides elevating intracellular cAMP levels elicited much weaker effects. AM rapidly reduced the gene transcript level of TNF-alpha, inducing a maximal effect within 1 h. The inhibitory effect of AM was restored with an AM receptor antagonist as well as a cAMP-dependent protein kinase inhibitor. These findings indicate that AM is a potent and quick suppressor of TNF-alpha production in Swiss 3T3 cells acting through the cAMP protein kinase A pathway. As TNF-alpha is a major inflammatory cytokine and stimulates AM production in fibroblasts, AM is deduced to be an autocrine or paracrine factor suppressing inflammation through the inhibition of TNF-alpha production.

3T3 Cells↗

Hyperalgesic response to noxious stimulation in genetically polydipsic mice.

Inbred mice, STR/N, are known to exhibit extreme polydipsia and polyuria but no abnormality in the response to exogenous vasopressin (AVP) and renal functions. Our previous studies have revealed that the brain opioid system is involved in the polydipsia of these mice. We here report that the STR/N mice show a decrease in the nociceptive threshold and a low, anti-nociceptive sensitivity to opioid receptors agonists. The paw-withdrawal latency (PWL) on a hot-plate in the STR/N mice was significantly shorter than that in their controls (BALB/c and C3H mice). This hyperalgesia was not affected by water restriction. Subcutaneous (s.c.) injections of morphine (5 mg/kg) and a kappa-opioid receptor agonist, U50,488H (16 mg/kg) had no effect on the PWL in the STR/N mice, whereas the control mice prolonged PWL after administration of the opioids. However, the STR/N mice gained the ability to show morphine analgesia after up-regulation of the opioid system by repeated administration of naltrexone (s.c., 5 mg/kg) for 3 consecutive days. The results suggest that the anti-nociceptive function of the opioid system is down-regulated in STR/N mice as is observed in chronic morphine-treated animals.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

[Assessment of left ventricular function by 201Tl ECG-gated myocardial SPECT].

We applied the QGS program for LV function analysis (described by Germano, 1995) to a 201Tl SPECT study at rest, and estimated its accuracy. We performed 201Tl ECG-gated myocardial SPECT in 25 patients with ischemic heart disease under an acquisition time used in the routine 99mTc ECG-gated SPECT study. The quality of the gated images was visually assessed with a 4-point grading system. LVEDV, LVESV, LVEF determined by the QGS program were compared with those by Simpson's method on biplane LVG in 25 patients. Regional wall motion scores in 7 myocardial segments were assessed on the three-dimensional display created by the QGS program and the cine display of biplane LVG with a 5-point grading system. Wall motion scores obtained by the QGS program were compared with those by LVG. Although 72.0% of 201Tl ECG-gated SPECT images were fair or poor in image quality, there were good correlations between the values obtained by the QGS program and LVG (LVEDV: r = 0.82, LVESV: r = 0.88, LVEF: r = 0.89). In addition, wall motion scores by the QGS program were correspondent to those by LVG in 77.1% of all 175 myocardial segments. We conclude that the QGS program provides high accuracy in evaluating left ventricular function even from 201Tl ECG-gated myocardial SPECT data.

Aged↗

Production of adrenomedullin in macrophage cell line and peritoneal macrophage.

We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-gamma (IFN-gamma) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7-fold after 14 h incubation. RA exerted a synergistic effect when administered with TPA, LPS, or IFN-gamma, whereas IFN-gamma completely suppressed AM production in RAW 264.7 cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-beta dose-dependently suppressed AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells, whereas AM suppressed the secretion of TNF-alpha and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented, and the secreted AM is deduced to function as a modulator of cytokine production.

Adrenomedullin↗

Adrenomedullin production in fibroblasts: its possible function as a growth regulator of Swiss 3T3 cells.

In addition to endothelial cells and vascular smooth muscle cells, we demonstrated that adrenomedullin (AM) is synthesized and secreted from fibroblasts, Swiss 3T3, Hs68, and NHLF cells, in a native and biologically active form. Synthesis and secretion of AM from these fibroblasts was regulated by inflammatory cytokines, such as tumor necrosis factor and interleukin-1, lipopolysaccharide, growth and differentiation factors, and hormones in a manner similar to that of vascular smooth muscle cells and endothelial cells. Tumor necrosis factor-alpha, interleukin-1beta, and dexamethasone elevated AM secretion, whereas transforming growth factor-beta1 and interferon-gamma suppressed it in these three fibroblasts. Swiss 3T3 cells were shown to express receptors specific for AM by both cAMP production and receptor binding assay, and AM was found to stimulate DNA synthesis of quiescent cells through the cAMP-mediated pathway. AM secreted from Swiss 3T3 cells was also confirmed to augment cAMP production and DNA synthesis in the cells themselves. These effects were inhibited by a neutralizing monoclonal antibody against AM. These findings raise the possibility that AM functions as a growth regulator in the case of Swiss 3T3 cells. As AM receptors are widely distributed, AM secreted from fibroblast may play a role as a local regulator in mesenchymal cells of inflammatory or wounded regions.

3T3 Cells↗

Sequential relationship between actions of CRF and PGE2 in the brain on splenic sympathetic nerve activity in rats.

An infusion of corticotropin-releasing factor (CRF, 0.1-5.0 micrograms/10 microliters/rat) into the third cerebral ventricle (i.c.v.) for 10 min increased the splenic sympathetic nerve activity in a dose-dependent manner in urethane + alpha-chloralose anesthetized rats. No changes in the arterial blood pressure and body temperature were observed. The CRF (1.0 micrograms/10 microliters)-induced enhancement of the splenic sympathetic nerve activity was completely blocked by an i.c.v. pretreatment with a CRF antagonist, alpha-helical CRF9-41 (alpha-hCRF, 10 micrograms/10 microliters). The increase in the splenic sympathetic nerve activity induced by CRF was not blocked by pretreatment with a cyclooxygenase inhibitor, sodium salicylate (100 micrograms/10 microliters). In contrast, the splenic sympathetic nerve activity also increased after an i.c.v. injection of prostaglandin E2 (PGE2, 1 ng/10 microliters) and the increase was completely blocked by i.c.v. pretreatment with alpha-hCRF. These findings suggested a sequential relationship between actions of CRF and PGE2, with an activation of PGE2 system followed by that of CRF system in the brain resulting in an increase in the splenic sympathetic nerve activity.

Animals↗