Biomedical subjects

T Morimoto

Publications and source records attributed to T Morimoto.

At least 127 records · Page 7Linked to original sources

PubMed1999

Application of intravascular ultrasonography for intracaval tumor thrombectomies in adrenal metastasis from hepatocellular carcinoma: report of two cases.

Intracaval tumor thrombus is one of the characteristic features of advanced hepatocellular carcinoma. To formulate an appropriate operative strategy for removing intracaval tumor thrombi, it is of great importance to accurately diagnose the location, any invasion into the wall of the vena cava, and the extent of intracaval tumor spread. Intravascular ultrasonographic imaging is a novel technology that enables the precise catheter-based assessment of the dimensions and morphology of the vascular structure and any lesions. We have applied this technology to the diagnosis of intracaval tumor thrombi originating from adrenal metastasis secondary to hepatocellular carcinomas. This modality was thus found to be useful in determining the best operative procedure for removing tumor thrombi in the inferior vena cava.

Adrenal Gland Neoplasms↗

PubMed1999

The effect of graft perfusion with warm blood cardioplegia for cadaver heart transplantation.

This study was designed to verify the effect of reperfusion of donor hearts in a perfusion apparatus after 60 min of global ischemia prior to heart transplantation. Thirteen dogs were exsanguinated from the femoral artery and cardiac arrest was achieved. The hearts were left in situ at room temperature (25 degrees C) for 60 min. In group A (n = 7), the hearts were excised and reperfused 60 min after cardiac arrest in the perfusion apparatus with substrate-enriched warm blood cardioplegia (WBCP) containing a hydroxyl radical scavenger, EPC, followed by 45 min of blood perfusion. Next, the hearts were preserved in cold (4 degrees C) University of Wisconsin (UW) solution. In group B (n = 6), the hearts were perfused with cold (4 degrees C) St. Thomas' solution 60 min after cardiac arrest and preserved in cold UW solution. Thereafter, all hearts in both groups were transplanted orthotopically to recipient dogs. In group A, 6 of 7 dogs were weaned from cardiopulmonary bypass (CPB). In group B, only 2 of 6 dogs were weaned from CPB. Moreover, 3 of the 6 hearts in group B did not start beating after transplantation (stone heart). This study suggested reperfusion of the donor heart in the perfusion apparatus with WBCP to be a beneficial preconditioning method when utilizing 60-min arrested hearts for transplantation.

Animals↗

PubMed1999

Right hepatic lobectomy for hepatocellular carcinoma which developed in primary biliary cirrhosis: report of a case.

The case of a 74-year-old female patient who underwent a right hepatic lobectomy for hepatocellular carcinoma (HCC) which developed in primary biliary cirrhosis (PBC) is reported herein. During a follow-up examination for Parkinson's disease, an elevation of hepatobiliary tract-related enzymes and alpha-fetoprotein was uncovered. Diagnostic imagings showed a hypervascular, solitary, and encapsulated tumor measuring about 7 cm in diameter located mainly in the posterior segment. Positive antimitochondrial and antinuclear antibodies and a preoperative liver biopsy strongly suggested well differentiated HCC developed in PBC (Scheuer's classification stage II). Since the natural prognosis of PBC estimated by the Mayo risk score was fairly good and the liver function indicated sufficient tolerance for major hepatic resection, and preoperative computed tomography (CT) volumetry showed the atrophy of the right hepatic lobe, a right hepatic lobectomy was performed. A pathological examination revealed well encapsulated, moderately differentiated HCC with, in part, well-differentiated HCC in the tumor and stage II PBC in the noncancerous region. CT volumetry performed at postoperative day 14 showed a 146% enlargement of the remnant liver. An early detection of HCC and PBC by strict screening would prevent a limitation of surgical therapy due to a deteriorated liver function.

Aged↗

PubMed1999

Case of intraductal papillary mucinous tumor (noninvasive adenocarcinoma) of the pancreas resected 27 years after onset.

A case of intraductal papillary mucinous tumor (IPMT) of the pancreas resected 27 yr after onset is presented. In March of 1997, a 71-yr-old man was admitted to our hospital with a complaint of severe epigastric pain. He had initially undergone endoscopic retrograde pancreatography (ERP) in April 1971 in our hospital and the patient had been followed up for pancreatografic changes for 26 yr. Dilatation of the main pancreatic duct gradually progressed during follow-up, and the filling defect owing to the tumor became demonstrable. On admission, ERP revealed diffuse dilatation of the main pancreatic duct, which was 20 mm in diameter, and the filling defect of 35 mm in diameter. We diagnosed this patient as having an IPMT of the pancreas. Considering his general condition, pancreatic segmentectomy was carried out, and the postoperative course was favorable. Histological findings were compatible with those of noninvasive papillary adenocarcinoma. This is a precious case for studying the natural history of intraductal papillary tumor of the pancreas and to evaluate the application of surgery, because the biologic behavior of this tumor is much less aggressive than that of pancreatic ductal cell carcinoma.

Adenocarcinoma↗

PubMed1999

Plastic surgical reconstruction of left main coronary artery.

OBJECTIVE(S): To report the early and mid-term results of surgical plasty of the left main coronary artery in 12 patients operated upon between 1993 and 1997. METHODS: The anterior approach was used in all patients. Saphenous vein (n = 4) of glutaraldehyde treated autologous pericardium (n = 8) were used as patch material. Additional coronary artery bypass grafting was performed in 7 patients, the first 3 as a safety back up, and for coexisting stenosis of other coronary branches not revascularized by the plastic procedure in the remaining 4. RESULTS: Pathologic specimens of the left main coronary artery in 5 revealed atheroma in 3 and myxomatous intimal thickening in 2. The left main coronary artery was widely patent angiographically in all patients prior to discharge. Six patients consented to angiographic restudy 5-40 months after the procedure and revealed excellent results in 5. One patient upon whom autologous pericardial patch had been used underwent percutaneous coronary angioplasty for restenosis of the left main coronary artery and a new lesion of the proximal left anterior descending branch 5 months after the operation. There were no late deaths nor other cardiac events. All patients were in CCS class 1 at their last follow-up. CONCLUSIONS: Surgical angioplasty of the left main coronary artery could be used to revascularize the left heart safely in patients with a discrete localized lesion of the left main coronary artery and is particularly useful in the face of unavailability of other conduits.

Aged↗

PubMed1999

New simple technique for hepatic parenchymal resection using a Cavitron Ultrasonic Surgical Aspirator and bipolar cautery equipped with a channel for water dripping.

We have developed a new technique to resect hepatic parenchyma without inflow occlusion by using the Cavitron Ultrasonic Surgical Aspirator (CUSA) and bipolar cautery with a saline irrigation system. The significance of this method in hepatectomy was analyzed in comparison with historical control of hepatectomy using Pringle's maneuver. An ordinary bipolar cautery was remodeled with an infusion line to bring saline droplets down the inner surface of one arm of the tweezers through an opening about 1.5 cm proximal to its tip. The optimal flow rate of saline was approximately one drop per second. The power of bipolar cautery was adjusted to 50 watts. When the tweezer blades were approximated to 1 or 2 mm, saline droplets were directed to the tip of tweezers and could be immediately evaporated. After sonicating parenchymal cells, the tissue of small branches of Glisson's tree or small tributaries of the hepatic vein were coagulated by bipolar cautery. The coagulated cords were then easily cut by scissors. The impact of this technique on ordinary liver resections was evaluated by analyzing the postoperative clinical course in relation to the hepatic functional reserve necessary for major hepatectomy, duration of hepatectomy, and intraoperative blood loss. Hepatic resection without vascular occlusion using this technique could decrease the morbidity in patients who have less hepatic functional reserve. It could also decrease intraoperative blood loss. This new technique effectively decreased the surgical load of the remnant liver during parenchymal resection by avoiding ischemic stress. Consequently it extends the safety limits of major hepatectomy.

Electrocoagulation↗

PubMed1999

Deaths from heat-stroke in Japan: 1968-1994.

Global warming is increasingly recognized as a threat to the survival of human beings, because it could cause a serious increase in the occurrence of diseases due to environmental heat during intermittent hot weather. To assess the direct impact of extremely hot weather on human health, we investigated heat-related deaths in Japan from 1968 through 1994, analyzing the data to determine the distribution of the deaths by age and their correlation to the incidence of hot days in summer. Vital Statistics of Japan, published by the Ministry of Health and Welfare of Japan, was the source of the heat-related mortality data employed in this study. Meteorological data were obtained from the District Meteorological Observatories in Tokyo and Osaka, the two largest cities in Japan. Heat-related deaths were most prone to occur on days with a peak daily temperature above 38 degrees C, and the incidence of these deaths showed an exponential dependence on the number of hot days. Thus, even a small rise in atmospheric temperature may lead to a considerable increase in heat-related mortality, indicating the importance of combating global warming. Furthermore, half (50.1%) of the above-noted deaths occurred in children (4 years and under) and the elderly (70 years and over) irrespective of gender, indicating the vulnerability of these specific age groups to heat. Since a warmer climate is predicted in the future, the incidence of heat waves will increase, and more comprehensive measures, both medical and social, should be adopted for children of 4 years and younger the elderly to prevent heat-related deaths in these age groups.

Adolescent↗

PubMed1999

Management of adrenal metastasis of hepatocellular carcinoma by asynchronous resection of bilateral adrenal glands.

We report on a 65-year-old man who received asynchronous bilateral adrenalectomy for adrenal metastasis of hepatocellular carcinoma. Fifteen months after curative resection of right hepatic lobe for hepatocellular carcinoma, a metastatic lesion of the left adrenal gland was detected and left adrenalectomy was performed. Ten months after the second operation, a metastatic lesion in the right adrenal gland, associated with tumor thrombus in the inferior vena cava, was revealed. Transcatheter arterial embolization of the arteries feeding the metastatic tumor was performed, but its effects were incomplete. As there was the tumor thrombus in the inferior vena cava and no other intrahepatic recurrence or extrahepatic metastasis was found, resection of the right adrenal gland with tumor thrombus, without the employment of veno-venous bypass, was performed, followed by postoperative hormonal supplementation. Changes in the patient's alpha-fetoprotein level were clinically useful for the detection of the metastatic lesions and the evaluation of therapeutic effects. Metastasis to adrenal gland from hepatocellular carcinoma should be actively managed, and the appropriate surgical treatment selected, if intrahepatic recurrence and/or other extrahepatic metastasis are controlled. To achieve higher curability and better outcome in patients with bilateral adrenal metastasis of hepatocellular carcinoma, bilateral total adrenalectomy is indicated, accompanied by effective postoperative hormonal supplementation.

Adrenal Gland Neoplasms↗

PubMed1999

Analysis of vitrectomy for idiopathic macular hole by optical coherence tomography.

PURPOSE: To evaluate foveal structure after vitrectomy for idiopathic macular hole in relation to postoperative visual outcome. METHODS: Optical coherence tomography was performed postoperatively to assess retinal thickness at the foveal center in patients who underwent vitrectomy, posterior hyaloid membrane removal, and perfluoropropane gas tamponade for idiopathic macular hole. Thirty-seven eyes of 36 patients documented to have achieved anatomic hole closure by optical coherence tomography were included in the study. RESULTS: Increased visual acuity significantly correlated with greater foveal thickness assessed at a median of 5 months postoperatively (Spearman analysis; R = .453, P = .005). CONCLUSION: Visual outcome after anatomic closure of macular holes by vitrectomy is closely related to the structure of the center of the fovea postoperatively.

Aged↗

PubMed1999

Involvement of the histaminergic system in leptin-induced suppression of food intake.

The ob gene product leptin is secreted from white adipose tissue, and may regulate food intake by acting on the hypothalamus in the central nervous system. But the mechanism of this effect is still unclear. The central histaminergic system has been suggested to participate in the control of various physiological functions, particularly in feeding behavior, as it mediates anorectic signals like leptin. Thus, we hypothesized that the central histaminergic system is a target for leptin in its control of feeding. To prove this, we first examined the effect of i.p. administration of alpha-fluoromethylhistidine (FMH), a specific and irreversible inhibitor of histidine decarboxylase, on leptin-induced suppression of food intake in normal C57BL strain mice. Leptin treatment (1.3 mg/kg, i.p.) significantly reduced food intake by 60% of that of control at 6 h and by 84% at 24 h compared with control. When mice were injected with FMH (100 mg/kg, i.p.) before being given leptin, leptin-induced suppression of food intake was abolished and there was no significant difference compared with that of control. Additionally, we further examined the effects of leptin on food intake in mutant mice lacking histamine H, receptors (H1R-KO mice). Leptin injection significantly reduced food intake by 56% of that of control at 6 h and by 79% at 24 h in wild-type mice (WT mice), but not in H1R-KO mice. This finding suggests that leptin affects the feeding behavior through activation of the central histaminergic system via histamine H1 receptors.

Animals↗

PubMed1999

Effect of parenteral and enteral nutrition on hepatic albumin synthesis in rats.

The route of nutrient delivery may alter the production of albumin and induce changes at the molecular level. Donryu rats (n = 75) were divided into the following three groups. The oral feeding (OR) group received a non-purified solid diet ad libitum, the parenteral nutrition (PN) group received a total parenteral nutrition (TPN) solution intravenously, and the enteral nutrition (EN) group received intragastric infusions of the TPN solution for 7 d. Serum albumin and glucocorticoid levels were measured and messenger RNA (mRNA) levels of albumin and hepatic specific transcription factors in the liver were analyzed. Serum albumin and albumin mRNA levels in the PN group became significantly decreased compared to those in the OR group, whereas the EN group did not show a significant difference compared to the OR group. mRNA levels of DBP, D-site binding transcription factor for the albumin gene, showed a circadian rhythm in the OR and EN groups, but not in the PN group, as indicated by a DBP mRNA level at 2200 h in the PN group that was significantly lower than that in the OR group. mRNA levels of C/EBP alpha, CCAAT-enhancer binding protein alpha, were highest in the OR group and lowest in the PN group. In contrast, mRNA levels of C/EBP beta were highest in the PN group and lowest in the OR group. Serum glucocorticoid level showed a circadian rhythm in the OR group, highest at 2200 h and lowest at 1000 h, whereas such a rhythm was not found in either the PN or the EN group. Albumin synthesis was down-regulated in PN in association with changes in transcription factors. A loss of circadian rhythm reflected in changes of DBP mRNA and serum glucocorticoid level may play a role. Down-regulation of albumin was improved by enteral feeding, indicating that EN is more advantageous for albumin synthesis than PN.

Animals↗

PubMed1999

Adenocarcinoma of the gastroesophageal junction in Japan: relevance of Siewert's classification applied to 177 cases resected at a single institution.

BACKGROUND: There had been a lack of international consensus about the definition of cancer of the gastric cardia until Siewert's classification was approved at a consensus conference during the second International Gastric Cancer Congress held in 1997. STUDY DESIGN: A review of the prospective gastric cancer database at Aichi Cancer Center from 1983 to 1992 identified 1,913 gastric carcinoma patients who underwent gastrectomy. These patients were classified retrospectively according to the Siewert classification, and 177 patients who fell into one of the three types form the basis of this study. Survival analyses were performed after stratifying patients by clinicopathologic variables. RESULTS: There were 33 patients with type II and 144 with type III, although none had type I, a type frequently observed in the west. No evidence of a change in the frequency of types II or III cancers (approximately 9.3% overall) among gastric carcinoma patients was observed over the 10-year period. Clinical staging of gastric carcinoma by the TNM classification was found to reflect accurately the prognosis of these patients. There were no longterm survivors among the few patients with metastasis to the perigastric nodes of the distal stomach. CONCLUSIONS: A striking difference in the distribution of types of adenocarcinoma of the gastroesophageal junction was observed in Japan compared with previously reported western data. A subgroup of carcinoma of the proximal stomach identified as types II and III may not require proximal gastrectomy from the viewpoint of sufficient lymphadenectomy.

Adenocarcinoma↗

PubMed1999

Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel.

CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1 in vivo, we generated mice lacking CLC-K1 by targeted gene disruption. Clcnk1-/- mice were physically normal appearance, but produced approximately five times more urine than Clcnk1+/- and Clcnk1+/+ mice. After 24 hours of water deprivation, Clcnk1-/- mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in Clcnk1+/- and Clcnk1+/+ mice, whereas only a minimal increase was seen in Clcnk1-/- mice, indicating nephrogenic diabetes insipidus. After in vitro perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in Clcnk1-/- mice in contrast to Clcnk1+/+ and Clcnk1+/- mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium.

Animals↗

PubMed1999

Role of interleukin-12 in the development of acute graft-versus-host disease in bone marrow transplant patients.

Interleukin-12 (IL-12) is a crucial cytokine regulating cell-mediated immunity, and may contribute to the development of graft-versus-host disease (GVHD). We investigated serum IL-12 concentrations, interferon gamma (IFN-gamma) production by peripheral blood lymphocytes (PBL) from allogeneic stem cell recipients after IL-12 plus anti-CD3 monoclonal antibody (mAb) stimulation. We also investigated IL-12 production by peripheral macrophages (Mphi) after lipopolysaccharide (LPS) stimulation from allogeneic stem cell recipients and patients receiving donor leukocyte transfusions (DLT) for treatment or prophylaxis of leukemia relapse and Epstein-Barr virus (EBV) lymphoproliferative disease (LPD). PBL from acute GVHD patients produced high IFN-gamma levels after IL-12 plus anti-CD3 mAb stimulation, whereas PBL from patients without acute GVHD produced low levels of IFN-gamma. However, serum IL-12 concentrations were low in both groups. Peripheral Mphi IL-12 production increased in patients who developed acute GVHD compared to patients without acute GVHD. Five patients receiving DLT for treatment or prophylaxis of leukemia relapse developed acute GVHD. IFN-gamma production by PBL stimulated by IL-12 plus anti-CD3 mAb increased, while IL-12 production by peripheral Mphi stimulated by LPS was very high after the development of acute GVHD. However, serum IL-12 concentration remained low. Three patients receiving DLT for EBV-LPD did not develop acute GVHD with no increase of IFN-gamma and IL-12 production. These results indicate that IL-12 may play an important role in the development of acute GVHD after allogeneic stem cell grafting or DLT, and increased IL-12 production by Mphi occurs with various stimuli, including LPS.

Acute Disease↗

PubMed1999

Characteristics of the daily lives of elderly women at various facilities for the elderly.

A number of studies have been conducted about support for the daily lives of elderly individuals that will elevate their quality of life (QOL). Services provided to support these individuals have also become more diverse. This study will attempt to add to the understanding of QOL for the elderly by comparing levels of dependence and QOL of elderly women in four different types of institution. Individuals who were over 65 years of age and who were able to participate in a 1 h interview were chosen for this study. The subjects were selected from the elderly population of a hospital for aged patients, health service facilities for the elderly, a nursing home and a general hospital. Levels of dependency of activities of daily living (ADL) were measured using the Kahoku Aging Longitudinal Study Scale. The scale qualitatively evaluates the cognition and activities of the elderly. Each measure is rated on a four point scale. Quality of life was measured using the visual analogue scale. Elderly women living at the nursing home differed from those living in the other facilities in regard to their degree of independence in ADL and QOL. These findings indicate that there were differences in the characteristics of the daily lives of elderly women at different types of facilities.

Activities of Daily Living↗

PubMed1999

Amino-terminal region of secreted form of amyloid precursor protein stimulates proliferation of neural stem cells.

Beta-amyloid precursor protein (APP) has been reported to be expressed in the CNS from the early stages of development. However, the functional role of APP during early development remains unclear. In the present study, we found that the secreted form of APP (sAPP) significantly enhanced proliferation of neural stem cells. Cells were prepared from 13-day embryonic rat neocortex, which was dissected with a Pasteur pipette to make cell clusters. After 12 h of cultivation in the medium without serum, cells around the centre of the cluster were still nestin-positive proliferative cells, i.e. neural stem cells. To determine whether the proliferation of cells was regulated by sAPP, cultures were treated with recombinant sAPP695, the secreted form of human APP695 produced by yeast. Both DNA synthesis and expression of proliferating cell nuclear antigen markedly increased after 5 h of sAPP695 addition. The enhancement of DNA synthesis by sAPP695 stimulation was blocked by the 22C11 monoclonal antibody specific for the amino-terminal region of sAPP. Then, we examined the effect of the amino-terminal fragment of sAPP and the epitope peptide of 22C11 antibody, and found that both of them also promoted DNA synthesis, suggesting that the amino-terminal region of sAPP is responsible for the biological activity. Our findings indicate the possibility that sAPP enhances proliferation of neural stem cells in vivo and plays an important role during the early CNS development.

Amyloid beta-Protein Precursor↗

PubMed1999

Effect of an exercise-heat acclimation program on body fluid regulatory responses to dehydration in older men.

We examined if an exercise-heat acclimation program improves body fluid regulatory function in older subjects, as has been reported in younger subjects. Nine older (Old; 70 +/- 3 yr) and six younger (Young; 25 +/- 3 yr) male subjects participated in the study. Body fluid regulatory responses to an acute thermal dehydration challenge were examined before and after the 6-day acclimation session. Acute dehydration was produced by intermittent light exercise [4 bouts of 20-min exercise at 40% peak rate of oxygen consumption (VO(2 peak)) separated by 10 min rest] in the heat (36 degrees C; 40% relative humidity) followed by 30 min of recovery without fluid intake at 25 degrees C. During the 2-h rehydration period the subjects drank a carbohydrate-electrolyte solution ad libitum. In the preacclimation test, the Old lost approximately 0.8 kg during dehydration and recovered 31 +/- 4% of that loss during rehydration, whereas the Young lost approximately 1.2 kg and recovered 56 +/- 8% (P < 0.05, Young vs. Old). During the 6-day heat acclimation period all subjects performed the same exercise-heat exposure as in the dehydration period. Exercise-heat acclimation increased plasma volume by approximately 5% (P < 0.05) in Young subjects but not in Old. The body fluid loss during dehydration in the postacclimation test was similar to that in the preacclimation in Young and Old. The fractional recovery of lost fluid volume during rehydration increased in Young (by 80 +/- 9%; P < 0.05) but not in Old (by only 34 +/- 5%; NS). The improved recovery from dehydration in Young was mainly due to increased fluid intake with a small increase in the fluid retention fraction. The greater involuntary dehydration (greater fluid deficit) in Old was accompanied by reduced plasma vasopressin and aldosterone concentrations, renin activity, and subjective thirst rating (P < 0.05, Young vs. Old). Thus older people have reduced ability to facilitate body fluid regulatory function by exercise-heat acclimation, which might be involved in attenuation of the acclimation-induced increase in body fluid volume.

Acclimatization↗

PubMed1999

Serotonergic modulation of the hyperpolarizing spike afterpotential in rat jaw-closing motoneurons by PKA and PKC.

Intracellular recordings were obtained from rat jaw-closing motoneurons (JCMNs) in slice preparations to investigate the effects of serotonin (5-HT) on the postspike medium-duration afterhyperpolarization (mAHP) and an involvement of protein kinases in the effects. Application of 50 microM 5-HT caused membrane depolarization and increased input resistance in the most cells without affecting the mAHP, whereas not only membrane depolarization and an increase in input resistance, but also the suppression of the mAHP amplitude was induced by higher dose of 5-HT (100 or 200 microM). On the other hand, when the mAHP amplitude was increased by raising [Ca(2+)](o) from 2 to 6 mM, 5-HT-induced attenuation of the mAHP amplitude was enhanced, and even 50 microM 5-HT reduced the mAHP amplitude. This 5-HT-induced suppression of the mAHP could be mimicked by application of membrane-permeable cAMP analogue 8-Bromo-cAMP, potentiated by the cAMP-specific phosphodiesterase inhibitor Ro 20-1724 and antagonized by protein kinase A (PKA) inhibitor H89. The enhancement of the mAHP attenuation induced by 50 microM 5-HT under raised [Ca(2+)](o) was blocked by a protein kinase C (PKC) inhibitor chelerythrine, suggesting an involvement of PKC in this enhancement. On the other hand, the attenuation of the mAHP induced by PKC activator phorbol 12-myristate 13-acetate was blocked almost completely by H89, suggesting that the PKC action on the mAHP requires PKA activation. Neither 5-HT(1A) antagonist NAN-190 or 5-HT(4) antagonist SB 203186 blocked 5-HT-induced attenuation of the mAHP. We conclude that 5-HT induces dose-dependent attenuation of the mAHP amplitude through cAMP-dependent activation of PKA and that PKC-dependent PKA activation is also likely to be involved in the enhancement of 5-HT-induced attenuation of the mAHP under raised [Ca(2+)](o). Because the slope of the linear relationship between firing frequency and injected current was increased only when the mAHP amplitude was decreased by 5-HT, it is suggested that the relation between incoming synaptic inputs and firing output in JCMNs varies according to serotonergic effects on JCMNs and calcium-dependent modulation of its effects.

Animals↗