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Biomedical subjects

H Takeuchi

Publications and source records attributed to H Takeuchi.

At least 325 records · Page 18Linked to original sources
PubMed1997

Pharmacological studies on YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT2A receptor antagonistic activity.

YM992 ((S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride) is a novel compound that has selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibition and 5-HT2A receptor antagonistic activity in vivo. YM992, fluoxetine and citalopram showed 5-HT uptake inhibition activity in l-5-hydroxy-tryptophan (l-5-HTP)-treated mice. YM992 and trazodone attenuated 5-HT2A/2C receptor agonist-induced head-twitches in mice, indicating that these drugs had 5-HT2A receptor antagonistic activity. YM992 and amitriptyline were highly active in the mouse tail suspension test. In contrast, fluoxetine and citalopram showed only a tendency to reduce the immobility time. Single treatment with YM992 as well as trazodone and fluoxetine ameliorated the learning deficit of olfactory-bulbectomized rats, whereas citalopram and amitriptyline showed an ameliorative effect only after chronic treatment. Although YM992 has moderate affinity for alpha1-adrenoceptors, alpha1-adrenoceptor antagonism of YM992 in vivo was 10 times weaker than that of trazodone. These results demonstrate that YM992 has 5-HT uptake inhibition and 5-HT2A receptor antagonistic activity in vivo, and suggest that YM992 may be a novel antidepressant with high efficacy in clinical use.

Animals↗
PubMed1997

Lipid structure of cytotoxic granules in living human killer T lymphocytes studied by Raman microspectroscopy.

The structures of cytotoxic granules in interleukin-2-activated human killer T lymphocytes have been investigated by Raman microspectroscopy at a single cell level. The Raman spectra of granules share a common feature that lipid Raman bands are much stronger than the Raman bands due to protein, indicating that one of the main components of the granule is lipid. To analyze the lipid structures of individual granules, relationships between Raman spectra and structures have been examined for a series of triacylgycerols with varied degrees of acyl chain unsaturation. Analysis based on the relationships shows that the granulous lipid is characterized by a high content of cis C=C bond, which ranges from about 1.5 C=C bonds per acyl chain in isolated minor granules and to about 2.2 C=C bonds in clustering major granules. The highly unsaturated lipid of major cytotoxic granules is in sharp contrast to the moderately unsaturated (about one C=C bond per acyl chain) plasma membrane lipid. The large difference in lipid unsaturation between the granule and plasma membrane may have relevance to the role of granulous lipid in packaging cytotoxic proteins inside the granule and preventing them from attacking the killer lymphocyte itself.

Humans↗
PubMed1997

Synchronous multiple colorectal adenocarcinomas.

BACKGROUND: The object of the present work was to characterize clinical features and the quality of preoperative examinations in patients with synchronous colorectal carcinomas, and to compare the incidence of associated benign polyps with our findings in patients with a single malignant lesion. METHODS: A retrospective evaluation of 225 patients with primary colorectal carcinoma revealed 9 cases (4.0%) of synchronous colorectal carcinomas. RESULTS: The synchronous colorectal carcinomas were located in the same anatomical segment in 7 patients and were divided into different segments in 2 patients. The accuracy of preoperative diagnosis was 55.6% by endoscopy alone and 66.7% by double contrast barium enema (DCBE) alone, while the rate was 77.8% when colonoscopy and DCBE were combined. There was a higher incidence of associated benign polyps in the group with synchronous colorectal carcinomas (55.6%) versus 28.7% for a single carcinoma (P < 0.05). The main reason why multiple lesions could not be identified preoperatively was that the distal lesions prevented examination of the proximal lesions. CONCLUSIONS: At the time of surgical resection, it is important to ascertain preoperatively whether or not a second lesion exists. If synchronous polyps are present in patients with synchronous colorectal carcinomas, they should be ablated to reduce the risk of metachronous colorectal carcinoma.

Adenocarcinoma↗
PubMed1997

Epithelial differentiation in intraspinal meningiomas.

To investigate the epithelial features of intraspinal meningiomas, 25 intraspinal meningiomas and 25 intracranial meningiomas were examined for the presence of pseudopsammoma bodies with hematoxylin-eosin and periodic acid-Schiff staining. In addition, we investigated the expression of keratin and epithelial membrane antigen (EMA) by immunohistochemical methods. Pseudopsammoma bodies were found in 3 of 25 cases of intracranial meningiomas (12%), but no definitive pseudopsammoma bodies were observed the intraspinal meningiomas. Three cases (12%) of intraspinal meningiomas and 9 cases (36%) of intracranial meningiomas, including 3 cases with pseudopsammoma bodies, were immunoreactive for keratin. All 25 (100%) intracranial meningiomas and 20 of 25 (84%) intraspinal meningiomas were reactive for EMA. In the intraspinal meningiomas, 4 of 25 cases (16%) showed no reactivity for EMA. These findings suggest that the origin of certain cell components of meningiomas may be different according to the site of the tumor or that the nature of meningioma may be modified by the local environment.

Aged↗
PubMed1997

Acute effects of pioglitazone on glucose metabolism in perfused rat liver.

Pioglitazone, a thiazolidinedone derivative, decreases insulin resistance and improves hyperglycemia in insulin-resistant obese and/or diabetic animals. However, the mechanisms by which hyperglycemia is improved are not well defined. We investigated the effects of pioglitazone on hepatic glucose metabolism using a perfused rat liver model. Perfusion with the buffer containing 1-10 microM pioglitazone for 20 min dose-dependently increased the hepatic fructose 2,6-bisphosphate content, a potent activator of 6-phosphofructo 1-kinase. The fructose 2,6-bisphosphate level after 20 min perfusion with 10 microM pioglitazone was 64.9 +/- 14.5 pmol/mg.protein, significantly higher than the control (48.3 +/- 10.9 pmol/mg.protein). When the liver from a starved for 48 h rat was perfused with the buffer containing 2 mM lactate but no glucose, glucose was generated from lactate via the gluconeogenic pathway and flowed into the effluent perfusate at a constant rate of 31 +/- 0.6 mumol/g.liver/h. The addition of 10 microM pioglitazone decreased the glucose output rate to 19.3 +/- 3.8 mumol/g.liver/h. Dose-dependent inhibition of glucose output by pioglitazone was observed in the 1-10 microM dose range. These results indicate that pioglitazone may not only stimulate glycolysis but also inhibit gluconeogenesis in the liver. These acute and insulin-independent effects on hepatic glucose metabolism may partly account for the diverse anti-diabetic effects of pioglitazone.

Administration, Oral↗
PubMed1997

Detection of latent Epstein-Barr virus (EBV) DNA in paraffin sections of nasopharyngeal carcinomas expressing no EBV-encoded small RNAs using in situ PCR.

In situ hybridization (ISH) with EBER 1 (Epstein-Barrvirus (EBV)-encoded small RNA1) probes is widely used for in situ detection of EBV-infected cells. ISH with an EBER1 probe showed that 10 of 40 NPC cases were negative for EBER1 expression. For in situ detection of EBV DNA, we used in situ PCR method which can detect one copy of EBV DNA per cell. Of the 10 EBER1-negative cases, three cases including one each of well- and poorly differentiated carcinomas and undifferentiated carcinoma were EBV DNA-positive by in situ PCR. The remaining seven were truly negative for the presence of EBV DNA. All the EBV genome-negative NPC cases examined here were histologically classified as poorly differentiated or undifferentiated carcinomas which are known to be closely associated with EBV, indicating the existence of EBV DNA-negative NPC cases, regardless of histological type or differentiation. These results indicate that there are EBV genome-positive NPC cases expressing no EBER1 and that in situ PCR can be suitable for in situ detection of EBV-infected cells, especially those expressing no EBER1 in paraffin sections.

Antisense Elements (Genetics)↗
PubMed1997

Immunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis, and psoriasis: possible implications for individual therapeutic efficacy.

BACKGROUND: In organ transplantation, patients with peripheral blood mononuclear cells (PBMCs) that exhibit resistance to cyclosporine (INN, ciclosporin) or glucocorticoids in vitro are refractory to therapy based on these drugs in vivo. However, detection or distribution of the resistant patients with immunologic disorders remains to be documented. METHODS: Drug sensitivity tests were performed with PBMCs from four subject groups: 69 healthy subjects, 100 patients with chronic renal failure, 38 patients with nephrosis, and 51 patients with psoriasis. The values for the concentration that produces 50% lymphocyte-mitosis inhibition (IC50) of the drugs on PBMC blastogenesis were estimated, and individual variations or group differences in the IC50 values were examined. RESULTS: The median cyclosporine IC50 values of the four subject groups were similar, but large individual deviations in the IC50 values were observed. Individual differences in prednisolone IC50 values were spread from 1 to 3500 ng/ml. When compared with healthy subjects, a significantly large number of the patients with chronic renal failure group exhibited low responses to prednisolone (p < 0.04). In contrast, no significant difference in the methylprednisolone IC50 was observed among the groups. Normal upper thresholds for IC50 values of these drugs were estimated from the mean + 2 standard deviations (SD) of the IC50 values of healthy PBMCs, and the patients with IC50 values above these levels were considered to be resistant. The incidence of resistant patients with nephrosis or psoriasis was similar to that of healthy subjects; however, the incidence of cyclosporine- or prednisolone-resistant subjects with chronic renal failure was significantly higher (p < 0.04). Significant correlations between PBMC sensitivity to cyclosporine in vitro and clinical efficacy of the drug in vivo were observed in renal transplant recipients and in patients with psoriasis. CONCLUSIONS: A large subset of patients with chronic renal failure showed PBMC resistance to cyclosporine and prednisolone. Hyperresistant patients have a high risk of being refractory to immunosuppressive therapy with one of these drugs. Alternative treatment should be considered according to the individual drug-sensitivity data.

Adult↗
PubMed1997

Prediction of recurrence in histologically benign meningiomas: proliferating cell nuclear antigen and Ki-67 immunohistochemical study.

BACKGROUND: Recurrence in individual patients after complete surgical removal of meningiomas cannot be predicted by histology alone because recurrence occurs even in histologically benign meningiomas. METHODS: We investigated proliferating cell nuclear antigen (PCNA) and Ki-67 labeling indices of histologically benign meningiomas in 95 patients to assess their relationship to recurrence. The labeling index (LI) was expressed as the percentage of tumor cell nuclei immunoreactive for PCNA or Ki-67 to total tumor nuclei counted per section. The cases/specimens comprised the following two groups: (1) nonrecurrent group: 82 specimens from 82 patients without recurrence, (2) recurrent group: 28 specimens from 10 patients with recurrence. RESULTS: Proliferative activities or aggressiveness do not always develop with every recurrence in recurrent meningiomas. The PCNA LI was significantly higher in the recurrent group (3.98% +/- 0.37%) than in the nonrecurrent group (0.71 +/- 0.13%) (p < 0.0001). The Ki-67 LI also was significantly higher in the recurrent group (3.15 +/- 0.40%) than in the nonrecurrent group (0.39 +/- 0.07%) (p < 0.0001). There was a good correlation between the PCNA LI and the Ki-67 LI (coefficient of correlation r = 0.79, p < 0.001). CONCLUSIONS: The results of our study suggested that a PCNA or Ki-67 LI of more than 2% may represent an increased risk for recurrence; therefore, we suggest that radiotherapy or stereotactic radiosurgery should be considered, even for histologically benign meningiomas.

Adolescent↗
PubMed1997

In vivo study of a calcium phosphate cement consisting of alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide.

Prehardened calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted in rabbit mandibles and back muscles, and studied histologically and microradiographically. In the mandibles, new bone formation occurred around the implants and increased in quantity the longer the implant period lasted. Histology, microradiography and scanning electron microscopy (SEM) demonstrated direct contact of bone and cement. Bone response to this cement was essentially the same as to hydroxyapatite (HA) ceramics, known as a biocompatible bone substitute. Material resorption was recognized, which increased with the implant period and was greater in the surface bound by soft tissue than the surface bound by bone tissue. In the back muscles, however, no calcified tissue formation occurred. Resorption proved to be faster than in the case of the mandible implants. It was concluded that the cement, in prehardened form, has good biocompatibility and is a promising material as a bone substitute.

Animals↗
PubMed1997

Glucocorticoid-resistance in peripheral-blood lymphocytes does not correlate with number of affinity of glucocorticoid-receptors in chronic renal failure patients.

Glucocorticoid (GC) resistance in patients with chronic renal failure (CRF) seriously impairs successive GC therapy after renal transplantation. We examined the relationship between GC-receptor (GC-R) parameters in peripheral-blood mononuclear cells (PBMC) and PBMC resistance to GC in 21 CRF patients and 18 healthy subjects. Each subject group was divided into two subgroups according to PBMC sensitivity to prednisolone in a mitogen assay procedure; i.e., sensitive (IC50 < 381 ng/mL) and resistant (IC50 > 381 ng/mL) groups. In healthy subjects, the mean GC-R Bmax and Kd in quiescent PBMC of the GC-sensitive group were 2.89 +/- 1.23 fmol/10(6) cells and 4.00 +/- 2.24 nM, respectively. The Bmax in these subjects significantly increased to 6.61 +/- 2.02 (257.7 +/- 107.8%) after 24 h stimulation with concanavalin A (p < 0.01), while the Kd change was not significant. The GC-R Bmax and Kd in quiescent PBMC of the GC-resistant group were 5.33 +/- 1.37 fmol/10(6) cells and 3.20 +/- 1.39 nM, respectively. Both of these parameters, however, did not change significantly after mitogen stimulation. There was a significant negative correlation between IC50S of prednisolone and increase-ratios (post/pre ratio) of Bmax after mitogen stimulation (p < 0.05). In CRF patients, Bmax and Kd in quiescent PBMC of the GC-sensitive group were 6.04 +/- 2.35 fmol/10(6) cells and 3.49 +/- 1.72 nM, respectively, while those in PBMC of the GC-resistant group were 5.13 +/- 2.31 fmol/10(6) cells and 4.04 +/- 1.62 nM, respectively. The Bmax and Kd were not significantly changed after mitogen stimulation in both subgroups of CRF. Moreover, in contrast to healthy subjects, there was no correlation between IC50 and GC-R parameters in CRF. We concluded that, in healthy subjects, decreased PBMC capacity to amplify GC-R numbers in response to mitogen is correlated with GC resistance, whereas in CRF patients the resistant mechanism is not correlated with GC-R parameters. An unknown event might be involved in GC-resistance of CRF.

Adult↗
PubMed1997

Glucocorticoids and cyclosporine induce apoptosis in mitogen-activated human peripheral mononuclear cells.

Induction of apoptosis by immunosuppressive agents such as glucocorticoids (GCs) and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However, there are few studies which demonstrate the induction of apoptosis by these agents in the activation process of human peripheral blood mononuclear cells (PBMCs). Here we show that potent immunosuppressive GCs and CsA induce apoptosis in concanavalin A (con A)-activated human PBMCs. In this study, GCs and CsA suppressed human PBMC-blastogenesis when activated by con A in a dose-dependent manner, where healthy PBMCs treated with > 100 ng/ml of each immunosuppressive agent exhibited a DNA-ladder structure in electrophoretic analysis. In three chronic renal failure (CRF) patients, dose-dependency of the PBMC-apoptosis induction was confirmed by our quantification of fragmented DNA using ELISA. Furthermore, the enrichment of DNA fragmentation was significantly associated with the rate of PBMC-blastogenesis when treated with GCs or CsA (r = -0.466, P < 0.01). These results suggested that suppression of the mitogen-induced PBMC-blastogenesis by the immunosuppressive agents should be correlated with the induction of apoptosis.

Apoptosis↗
PubMed1997

Enhanced amplitude reduction of somatosensory evoked potentials by voluntary movement in the elderly.

We studied the effects of aging on modification of the median nerve somatosensory evoked potentials (SEPs) by voluntary movement in 17 aged (66.5 +/- 8.9 years, mean +/- SD) and 12 young normal humans (27.5 +/- 5.0 years). The amplitudes of cortical SEP components were generally larger in the aged group than in the young group. Following isometric contraction of the thenar muscle, the aged group showed significant attenuation of the prerolandic P22-N28-P45 and the postrolandic P24-N30-P45, while the young group only demonstrated significant reduction of the prerolandic P22-N28 amplitude. In the prerolandic N28-P45 and the postrolandic P24-N30 and N30-P45, amplitudes reduced by voluntary movement (gated amplitude) significantly correlated with amplitudes at rest (resting amplitude) and with the age of subjects. The effects of stimulus intensity and frequency on gating supported the correlative changes between gated and resting amplitudes. These results suggest that the magnitude of gating depends on SEP amplitudes at rest, and that augmented gating in the aged group is a result of enlarged SEPs. Since the cervical and Erb's potentials were not changed by movement, and passive movement did not significantly affect the SEPs, a centrifugal mechanism is probably responsible for gating in this study.

Adult↗
PubMed1997

Pharmacologic characteristics of excitatory gamma-amino-butyric acid (GABA) receptors in a snail neuron.

1. The pharmacologic characteristics of excitatory gamma-aminobutyric acid (GABA) receptors, termed muscimol II type GABA receptors, found in a giant neuron type, v-LCDN (ventral-left cerebral distinct neuron), of an African giant snail (Achatina fulica Férussac), were studied using the mammalian GABA receptor agonists, antagonists and synergists and GABA uptake inhibitor using the voltage clamp technique. 2. GABA and its agonists, ejected by brief pressure, produced an inward current (Iin) of the following order of potency: trans-t-aminocrotonic acid (TACA) > GABA > muscimol > isoguvacine > 5-aminopentanoic acid and cis-4-aminocrotonic acid (CACA). (+/-)-Baclofen and 3-aminopropylphosphonic acid (APPA) were ineffective. The Iin values produced by GABA, TACA, isoguvacine and CACA were stable for at least 60 min, whereas the Iin induced by muscimol was not. 3. According to the dose-response curves of GABA, TACA, isoguvacine and CACA, measured by the varied pressure duration method, the ED50 value of CACA was larger than those of the other compounds, and Emax of TACA was larger than that of GABA, whereas Emax values of isoguvacine and CACA were smaller. 4. The perfusion of beta-alanine, pentobarbital and 5-aminopentanoic acid inhibited the Iin induced by GABA, whereas (-)-bicuculline, pitrazepin, diazepam and 2-hydroxysaclofen had no effect. 5. From the effects of beta-alanine on the dose-response curves of GABA, measured by the varied pressure duration method, beta-alanine competitively inhibited the Iin caused by GABA. According to the effects of pentobarbital on the dose-response curves of GABA, this drug noncompetitively inhibited the Iin using the varied pressure duration method, and partly competitively and partly noncompetitively using the Y-tube method. The effects of 5-aminopentanoic acid on the dose-response curves of GABA indicated that this drug noncompetitively inhibited the Iin using the varied pressure duration method, and partly noncompetitively and partly uncompetitively using the Y-tube method. 6. The pharmacologic features of the Achatina muscimol II type GABA receptors were similar to those of mammalian GABAC (GABAp1) receptors, except for the effects of pentobarbital.

Animals↗
PubMed1997

Synthesis of achatin-I (Gly-D-Phe-L-Ala-L-Asp) analogs having dehydrophenylalanine or aminoisobutyric acid residue at position 2, and their effects on Achatina giant neurons.

1. Achatin-I (Gly-D-Phe-L-Ala-L-Asp), a neuroactive tetrapeptide having a D-phenylalanine residue, has been proposed to be an excitatory neurotransmitter of Achatina giant neurons. It was revealed that the D-Phe2 residue is essential for bioactivity of achatin-I, which seems to adopt beta-turn conformation. In the present study, in order to investigate the structure-activity relationships of achatin-I and its derivatives, the two highly constrained analogs of achatin-I, [delta ZPhe2]achatin-I (Gly-delta ZPhe-L-Ala-L-Asp) (delta ZPhe: (Z)-alpha,beta-dehydrophenylalanine) and [Aib2]achatin-I (Gly-Aib-L-Ala-L-Asp) (Aib: alpha-aminoisobutyric acid), were synthesized, and their effects on the two identifiable Achatina giant neuron types, PON (periodically oscillating neuron) and v-RCDN (ventral-right cerebral distinct neuron), were examined in comparison with those of achatin-I under voltage clamp. 2. Achatin-I (n = 6), ejected onto the neurone by brief pneumatic pressure (2 kg/cm2, 400 ms, 10(-3) M, at 10-min intervals), produced an inward current (Im) on PON. The Iin value (mean +/- SEM) was 0.44 +/- 0.03 nA. The interval between the achatin-I ejection and the Iin peak was 14.74 +/- 3.15 s (n = 6). [delta ZPhe2]achatin-I (n = 6) and [Aib2]achatin-I (n = 6) had no effect on this neuron type. 3. On the other hand, achatin-I (n = 10) and [delta ZPhe2]-achatin-I (n = 10), ejected by brief pressure, produced an Iin on v-RCDN. The Iin values were 0.85 +/- 0.07 nA for achatin-I and 0.48 +/- 0.05 nA (p < 0.01, compared with that of achatin-I by Student's t-test for paired data) for [delta ZPhe2]achatin-I. The intervals between the compound ejection and the Iin peak were 5.95 +/- 0.33 s for achatin-I and 8.70 +/- 0.81 s (p < 0.05, compared with that of achatin-I) for [delta ZPhe2]achatin-I. [Aib2]achatin-I (n = 10) had no effect on this neuron type.

Animals↗
PubMed1997

Ouabain-sensitive K(+)-dependent outward current caused by threo-beta-hydroxy-L-glutamic acid on a snail neuron.

1. An analog of L-glutamic acid, threo-beta-hydroxy-L-glutamic acid (threo-L-BHGA), was applied locally to the giant neuron of an Achatina snail by pneumatic brief pressure ejection and induced an outward current (Iout) on the ventral-left cerebral distinct neurone (v-LCDN). The present study aimed to elucidate the ionic mechanisms of the Iout caused by threo-L-BHGA (ItL-BHGA) of v-LCDN and the effects of ouabain on this current under voltage clamp. 2. The reversal potentials of ItL-BHGA (EtL-BHGA) of v-LCDN in varied K+o were fitted to the Nernst equation as ItL-BHGA = IK (K+ current) and were almost unchanged in Cl-o-free and Na+o-reduced (20% of normal) states. The ItL-BHGA is due to the increase in permeability of the neuromembrane to K+(K(+)-dependent) and is neither Na(+)- nor Cl-(-)-dependent. K(+)-channel blockers, a mixture of tetraethyl-ammonium (TEA) and 4-amino-pyridine (4-AP), blocked ItL-BHGA mainly in a noncompetitive and partly in an uncompetitive manner. 3. Unexpectedly, ItL-BHGA of v-LCDN was almost abolished in the Na+o-free state and significantly reduced in the Cl-o-free state. However, an Na(+)-channel blocker, tetrodotoxin, showed a tendency to enhance ItL-BHGA. On the other hand, ItL-BHGA was enhanced in K+o-free state. 4. Ouabain markedly inhibited ItL-BHGA in both noncompetitive and uncompetitive manners. Benzamil, an inhibitor of the Na(+)-Ca2+ exchange applied simultaneously with ouabain could not prevent ouabain inhibition on ItL-BHGA. The currents induced by other putative neurotransmitters, including a K(+)-dependent Iout caused by dopamine on v-LCDN, were not affected by ouabain. 5. According to our previous study, the threo-L-BHGA receptors are not linked with protein kinases or calmodulin. Then, ItL-BHGA could be produced by the receptor K+ channel complex or the receptor-G-protein-K+ channel combination. The present results indicate that the ATPase activity inhibited by ouabain and the presence of extracellular Na+ and Cl- are needed for threo-L-BHGA to activate the K(+)-dependent structure. Furthermore, the K+o-free state, which inactivates the Na(+)-K+ pump, and tetrodotoxin, which suppresses the Na+ channel at least partly, did not affect the structure to be activated.

4-Aminopyridine↗
PubMed1997

Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, of currents induced by neuroactive compounds on Achatina neurons: amines and amino acids.

1. Modulatory effects of APGW-amide (Ala-Pro-Gly-Trp-NH2), proposed as an inhibitory neurotransmitter of Achatina neurons, perfused at 3 x 10(-6) M on the currents induced by small-molecule putative neurotransmitters were examined by using Achatina giant neuron types, v-RCDN (ventral-right cerebral distinct neuron), TAN (tonically autoactive neuron) and RAPN (right anterior pallial nerve neuron), under voltage clamp. These putative neurotransmitters were ejected locally to the neuron by brief pneumatic pressure. 2. Outward current (Iout) induced by erythro-beta-hydroxy-L-glutamic acid (erythro-L-BHGA) on v-RCDN, which was probably K+ dependent, was enhanced with membrane conductance (g) increase under APGW-amide. From dose (pressure duration)-response curves of erythro-L-BHGA measured in physiological solution (control curve) and with APGW-amide (drug curve), ED50 values of the two curves were nearly comparable, whereas Emax of the drug curve was significantly larger than that of the other. From a Lineweaver-Burk plot of these data, the cross point of the control line and the drug line was on the abscissa. 3. K(+)-dependent Iout caused by dopamine (DA) on v-RCDN was inhibited with a g increase by APGW-amide. The inhibition of this current caused by APGW-amide was mainly in a noncompetitive and partly uncompetitive manner. 4. 5-Hydroxytryptamine (5-HT) produced an inward current (Iin) with two (fast and slow) components on TAN, which was probably Na+ dependent. The fast component of the Iin was inhibited by APGW-amide. The inhibition was mainly in a noncompetitive manner. 5. The currents induced by acetylcholine, gamma-aminobutyric acid and L-glutamic acid on Achatina neuron types were not affected by APGW-amide. 6. The inhibitory effects of APGW-amide on the Iin (fast component) induced by 5-HT were nearly equipotent or a bit stronger than those on the Iout caused by DA. 7. The g increase produced by APGW-amide would be a cause for inhibiting the Iout induced by DA. In addition, we consider that APGW-amide affects intracellular signal transduction systems or ionic channels, thus modulating these currents.

Animals↗
PubMed1997

Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, of currents induced by neuroactive compounds on Achatina neurons: peptides.

1. Modulatory effects of APGW-amide (Ala-Pro-Gly-Trp-NH2), proposed as an inhibitory neurotransmitter of Achatina neurons, perfused at 3 x 10(-6) M on the currents induced by neuroactive peptides, ejected by brief pressure, were examined by using Achatina giant neuron types, v-RCDN (ventral-right cerebral distinct neuron) and PON (periodically oscillating neuron), under voltage clamp. 2. Outward current (Iout) caused by FMRFamide (Phe-Met-Arg-Phe-NH2) on v-RCDN, which was probably K+ dependent, was inhibited with membrane conductance (g) increase by APGW-amide. From the dose (pressure duration)-response curves of FMRFamide and a Lineweaver-Burk plot of these data, the inhibition caused by APGW-amide was mainly in an uncompetitive manner. 3. Iout caused by APGW-amide on v-RCDN, which was probably K+ dependent, was inhibited with g increase by APGW-amide. The inhibition caused by APGW-amide was partly in a competitive manner and partly in a noncompetitive manner. 4. Iout caused by [Ser2]-Mytilus inhibitory peptide, [Ser2]-MIP (Gly-Ser-Pro-Met-Phe-Val-NH2) on v-RCDN, which was probably K+ dependent, was inhibited with g increase by APGW-amide. Because the modulation of this current was not so marked, a dose-response study of this compound was not carried out. Iin induced by oxytocin on PON was not affected by APGW-amide. 5. From the dose-response curves of APGW-amide, perfused consecutively, the inhibitory effects of APGW-amide on the Iout caused by APGW-amide were stronger than those on the Iout caused by FMRFamide. 6. The inhibition of the APGW-amide-induced Iout on v-RCDN by APGW-amide was partly due to the competition in the receptor sites and partly to the g increase. The inhibition by APGW-amide on the Iout induced by FMRFamide and [Ser2]-MIP would be partly due to the g increase. In addition, we consider that APGW-amide affects intracellular signal transduction systems or ionic channels, thus modulating these currents. 7. The currents modulated by APGW-amide were different from those modulated by achatin-1, another Achatina endogenous neuroexcitatory peptide. We consider that the mechanisms underlying the modulatory effects of APGW-amide are different from those of achatin-I.

Animals↗