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H C Chung

Publications and source records attributed to H C Chung.

At least 55 records · Page 3Linked to original sources
PubMed1997

Intermittent bolus versus patient-controlled epidural morphine for postoperative analgesia.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) is a technique that combines the flexibility and convenience of PCA with the intrinsic analgesic efficacy of epidurally administered opioids. The aim of this study is to compare the analgesic and side effects of intermittent bolus injections of epidural morphine with PCEA using morphine during the first 24 h after elective low abdominal surgery. METHODS: Sixty patients were randomly assigned into two groups. Patients in group I (n = 30) received 3 mg epidural morphine at an 8-hour interval after surgery. Patients in group II (n = 30) received 2 mg epidural morphine after surgery and patient-controlled analgesia device was processed to deliver morphine 0.15 mg/h, 0.15 mg/bolus. All patients were observed for pain relief and adverse effects for 24 h. RESULTS: Mean morphine consumption was 9 mg for epidural morphine group and 6.87 +/- 0.27 mg for PCEA group. Although the PCEA group utilized significantly less morphine (p < 0.05), pain and sedation scores were similar in the two groups. Pruritus occurred more frequently in the epidural morphine group (63%) than in the PCEA group (33%). Frequency and severity of nausea and vomiting were similar in the two groups. CONCLUSIONS: PCEA with morphine decreases morphine consumption and with less adverse effects than intermittent bolus of epidural morphine. PCEA with morphine is an acceptable alternative to epidural morphine after low abdominal surgery.

Analgesia, Epidural↗
PubMed1997

Retention of broken central venous catheters in pulmonary artery and inferior vena cava--a case report.

Central venous catheterization (CVC) has become an important maneuver both for measuring the central venous pressure and for carrying out long-term intravenous alimentation. Furthermore, a central vein may be needed for the rapid restoration of blood volume in condition of acute hemorrhage with difficulties establishing of a peripheral cannulation. However, complications related to either the venipuncture or the presence of catheters in the central venous system were reported. The case we reported here had two ruptured catheter fragments retained in the great vessels, one in the right subclavian vein and the other one in the femoral vein during CVC. They migrated to the pulmonary artery and inferior vena cava, and were finally removed through open sternotomy with pulmonary arteriotomy and exploration of common iliac vein two weeks later. This was an unusual and possibly fatal complication.

Adult↗
PubMed1996

Sequential activation and production of matrix metalloproteinase-2 during breast cancer progression.

The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix metalloproteinases (MMPs) and serine proteases. We measured the activity of MMP-2 from 28 normal, 12 benign and 126 breast cancer tissues using gelatin zymography. Inactive MMP-2 (72 kD) was expressed in 53.6% of the normal and 66.6% of the cancer tissues, respectively (P = 0.77), while active MMP-2 (62 kD) was expressed in 28.6% and 73.0%, respectively (P = 0.003). The enzymatic activity of active MMP-2 (62 kD) measured in the gel band area was 4.0 +/- 7.2 mm2 in normal breasts, 7.7 +/- 9.8 mm2 in benign breast diseases, 9.5 +/- 8.5 mm2 in ductal carcinoma in situ (DCIS), and 12.0 +/- 13.7 mm2 in invasive cancers. The MMP-2 activation ratio (62 kD/62 kD + 72 kD) was 0.12 +/- 0.18 in normal tissues, 0.10 +/- 0.20 in benign diseases, 0.61 +/- 0.22 in DCIS, and 0.50 +/- 0.28 in invasive cancers. In conclusion, MMP-2 activation was the main cause of the increased 62 kD MMP-2 activity during the early phase of breast cancer, while production of MMP-2 supplemented the increased 62 kD activity in the late phase. We suggest, therefore, that these differential expressions of MMP-2 activation and production during the different stages of breast cancer progression are potential therapeutic targets for biological or gene therapy under the concept of stage-oriented cancer treatment.

Breast↗
PubMed1996

Gastric cancer in young patients who underwent curative resection. Comparative study with older patients.

Although several studies demonstrated the poor prognosis of young patients with gastric cancer, there were few reports about the survival of young patients who underwent radical surgery. We retrospectively reviewed the hospital records of 697 patients with curatively resected locally advanced gastric cancer to compare the pathologic findings and prognosis of young patients (aged < 40 years; 91 patients) with those of older (aged > or = 40 years; 606 patients) patients. There were no significant differences in location of tumors, Borrmann types, tumor invasion, and pathologic stage between both age groups. Despite the male predominance in older patients, the male-to-female ratio was nearly equal in young patients (p = 0.022). A significantly higher percentage of young patients showed poorly differentiated histology including signet ring cell and undifferentiated carcinoma than older patients (p < 0.0001). Adjuvant chemotherapy was more frequently performed in the young patients with a variety of different regimens (85.7 vs. 72.3%; p = 0.009). The 5-year overall survival rate revealed no statistically significant differences between the young and older patients (53.1 vs. 56.6%; p = 0.820). In conclusion, the young patients with curatively resected locally advanced gastric cancer showed similar survival compared to that of older patients.

Adult↗
PubMed1996

P-glycoprotein as an intermediate end point of drug resistance to neoadjuvant chemotherapy in locally advanced gastric cancer.

The expression of p-glycoprotein (p-gp) was evaluated in pre- and post-chemotherapy states after the administration of adriamycin-based chemotherapy in 24 gastric cancer patients. Among them, group A was composed of twelve patients who relapsed after surgery plus adjuvant chemotherapy and group B was composed of another twelve patients who received neoadjuvant chemotherapy plus surgery. Pre-chemotherapy p-gp was evaluated in 18 out of 24 patients (6 patients had no pre-chemotherapy paraffin blocks) and post-chemotherapy p-gp was evaluated from all 24 patients. Pre- and post-chemotherapy p-gp was expressed in 5 of 18 patients (27.8%), and 9 of 24 patients (37.5%), respectively, with immunohistochemical stain using monoclonal antibody JSB-1. No differences of disease-free survivals were observed in Group A based on post-chemotherapy p-gp expression from relapsed lesions. In Group B, there was a higher relapse rate (p = 0.04) and a lower one-year disease-free survival rate (p = 0.04) in post-chemotherapy p-gp positive patients when adjuvant treatment was done with the same regimen as neoadjuvant chemotherapy. In all patients studied, post-chemotherapy p-gp expression correlated with a higher systemic recurrence (p = 0.04). These data suggest that p-gp can be induced by an adriamycin-based chemotherapy in gastric cancer. Thus, we suggest that the prognosis of gastric cancer may be poor if a multidrug resistance (MDR)-related regimen is used in the presence of p-gp after neoadjuvant chemotherapy with an adriamycin-based regimen, even if the initial response is good.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Molecular mechanism for alkyl sulfide-modulated carbon tetrachloride-induced hepatotoxicity: the role of cytochrome P450 2E1, P450 2B and glutathione S-transferase expression.

The modulation of CCl4-induced hepatotoxicity in response to alkyl sulfides and alkyl ethers including allyl disulfide (ADS), allyl sulfide (AS), allyl ether (AE), propyl disulfide (PDS), propyl sulfide (PS), propyl ether (PE) and butyl sulfide (BS) was studied. Whereas pretreatment of rats with either ADS or AS (50 mg/kg, 7 days) blocked a CCl4-induced increase in plasma alanine aminotransferase (ALT) activity by 91 and 56%, respectively, AE, PDS, PS, PE or BS treatment enhanced CCl4-induced ALT activity by 52, 55, 238, 25 or 86%, respectively. Histochemical examinations supported the results of plasma ALT activity. Injection of GdCl3 to PS-pretreated rats failed to block the potentiated ALT increase, whereas GdCl3 completely prevented vitamin A-enhanced elevation of ALT activity. AS treatment completely blocked PS-potentiated CCl4 intoxication. Concomitant treatment of animals with both PS and vitamin A followed by a CCl4 insult resulted in super-potentiation of CCl4-induced hepatotoxicity, suggesting that the mechanism of PS-enhanced hepatotoxicity differs from that caused by vitamin A. Pyridine or phenobarbital potentiation of CCl4-induced increases in ALT activity implys that cytochrome P450 2E1 (P450 2E1) and P450 2B expression may be associated with the increased toxicity. P450 2E1 expression appeared to be associated with the alkyl sulfide-modulated hepatotoxicity, as evidenced by both immunoblot analyses and metabolic activity. P450 2B immunoblot analysis revealed that either AS or PS substantially induced hepatic P450 2B1/2 levels. Thus, PS-enhanced CCL4 hepatotoxicity may be related in part with P450 2B induction. ADS, AS or PS treatment caused increases in the glutathione S-transferase (GST) conjugating activity toward 1-chloro-2,4-dinitro-benzene. ADS, AS or PS induced Ya and Yb1 subunits by 2- to 3-fold. ADS or AS treatment also significantly elevated the levels of Yc subunits. PS failed to induce Yc expression, although this agent effectively increased Yb2 expression. Northern blot analyses revealed that ADS and AS concomitantly stimulated GST Ya, Yb1 and Yc2 gene expression, whereas PS increased the levels of Ya, Yb1, and Yb2 mRNA, but not Yc2 mRNA levels. The expression of GST subunit Yc2 in response to these compounds might be associated with hepatoprotective effects. These results demonstrate that ADS and AS have distinct capability of blocking CCl4-induced hepatotoxicity, whereas certain saturated alkyl sulfides rather potentiate CCl4-induced hepatotoxicity and that the underlying mechanism is associated with P450 2E1 and P450 2B expression, and possibly with certain GST expression.

Allyl Compounds↗
PubMed1995

Regulation of phosphatidylinositol kinases by arachidonic acid in rat submandibular gland cells.

Phosphoinositide kinases were characterized in membrane extracts of rat submandibular gland cells. Both phosphatidylinositol (PI) 4-kinase and phosphatidylinositol-4-phosphate (PI(4)P) 5-kinase phosphorylated endogenous substrates in reactions that were linear for up to 5 min, were activated by Mg2+ and showed maximal activity around neutral pH. PI 4-kinase was stimulated by Triton X-100 at an optimal concentration of 0.22%, but the detergent had an inhibitory effect on PI(4)P 5-kinase. Arachidonic acid (AA), at concentrations greater than 100 microM, inhibited the activity of both enzymes in a dose-dependent manner. The inhibitory effect was replicated by other unsaturated fatty acids, but not by a saturated fatty acid of the sn-20 series. The nature of AA inhibition of the kinases was examined in enzyme kinetic studies with exogenous phosphoinositide and adenosine 5'-triphosphate (ATP) substrates. Lineweaver-Burk plots of PI 4-kinase activity showed that AA had no effect on the apparent Km for either PI or ATP, but that the fatty acid significantly reduced Vmax (PI) from 331 to 177 pmol.mg-1.min-1 and Vmax (ATP) from 173 to 59 pmol.mg-1.min-1. This inhibitory action was consistent for PI(4)P 5-kinase kinetics, where again, AA did not alter apparent Km values, but lowered Vmax for both PI(4)P and ATP by around 50%. Since the combination of a reduced Vmax and an unchanged Km value indicates noncompetitive enzyme inhibition, it is proposed that AA regulates phosphoinositide cycle activity in submandibular gland cells by acting as a noncompetitive inhibitor of PI 4-kinase and PI(4)P 5-kinase.

1-Phosphatidylinositol 4-Kinase↗
PubMed1995

Muscarinic regulation of phospholipase D and its role in arachidonic acid release in rat submandibular acinar cells.

The characteristics of muscarinic cholinergic-induced phospholipase D (PLD) activation, and the involvement of the enzyme in the release of arachidonic acid were examined in rat submandibular acinar cells. Carbachol produced a dose-related activation of PLD to around fivefold control values at 100 microM agonist concentration. This was associated with the appearance of free choline, phosphatidic acid and arachidonic acid, indicating that the PLD substrate was phosphatidylcholine. The response to carbachol was inhibited by 60% by U73122, a blocker of a phospholipase C (PLC) specific to phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], suggesting that the cleavage of phosphatidylcholine by PLD was, at least in part, secondary to agonist-coupled hydrolysis of PtdIns(4,5)P2 by PLC. Consistent with this, PLD was also activated to levels comparable to those induced by carbachol, by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), and the Ca2+ mobilizer, thapsigargin, two agents that respectively mimic the activation of protein kinase C (PKC) by diacylglycerol and the elevation of cytosolic Ca2+ by inositol 1,4,5-triphosphate [Ins(1,4,5)P3] in the phosphoinositide effect. The cell-permeant Ca2+ chelator 1,2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA/AM) abolished the thapsigargin-induced activation of PLD and inhibited the responses of PLD to carbachol and TPA by 60%. The PKC inhibitor, Ro-31-8220, also inhibited the activation of PLD by carbacol and TPA to a level of approximately double control values, but had no effect on the thapsigargin-induced elevation of PLD. A role for both the PKC-associated and Ca(2+)-mobilizing arms of the PtdIns(4,5)P2-PLC pathway in PLD regulation is thus suggested. Pretreatment of cells with the phosphatidate phosphohydrolase blocker, propranolol, significantly enhanced the carbachol-induced elevation of phosphatidic acid, but decreased agonist-stimulated production of diacylglycerol and arachidonic acid, indicating that phosphatidlycholine was the likely source of arachidonic acid. We therefore propose that, in submandibular mucous acinar cells, muscarinic activation of the PtdIns(4,5)P2-PLC pathway regulates phosphatidylcholine-specific PLD through both the PKC- and Ca(2+)-mobilizing arms of the phosphoinositide response, and that diacylglycerol, derived from phosphatidylcholine via phosphatidic acid, is a source of free arachidonic acid.

Animals↗
PubMed1995

Enhanced effectiveness of dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate in combination with garlic oil against experimental hepatic injury in rats and mice.

The present study was designed to evaluate the effects of dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (PMC) in combination with garlic oil against chemical-induced hepatic injury in rats and mice. Rats insulted with carbon tetrachloride were concomitantly treated with PMC and/or garlic oil (50 and 100 mg kg-1, respectively) for four weeks. Whereas treatment of animals with garlic oil alone was ineffective in suppressing carbon tetrachloride-induced hepatotoxicity, administration of PMC in combination with garlic oil more effectively protected the liver against the carbon tetrachloride-induced insult than PMC alone, as monitored by serum aminotransferase activity. Hepatoprotective effects of the formulation were further supported by the changes in the numbers of Kupffer cells and dead hepatocytes. Although prior treatment of rats with PMC for three days failed to protect hepatotoxicity elicited by allyl alcohol, the formulation of PMC and garlic oil was capable of blocking allyl alcohol-induced hepatotoxicity by approximately 40%. To further examine the effect of the agents on lipid metabolism in the liver, hepatic triglycerides and cholesterol contents were assessed in mice after a diet containing PMC and/or garlic oil for one week followed by a single dose of carbon tetrachloride. Garlic oil appeared to be more effective in bringing hepatic lipid levels to those of control than PMC alone. Treatment of animals with PMC in combination with garlic oil synergistically improved chemical-induced impairment of hepatic triglycerides and cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Propanol↗
PubMed1995

Primary lymphoma of the thyroid.

Primary lymphoma presenting in the thyroid gland is uncommon. A review of the Yonsei University Medical Center experience between 1982 and 1994 was performed retrospectively to assess the treatment outcome and prognostic factors. There were four females and one male, and the median age was 65 years. All 5 cases presented with a neck mass. Two of them had co-existing biopsy-proved Hashimoto's thyroiditis and three cases were each in a hypothyroid state. All cases with non-Hodgkin's disease were of intermediate grade. One case was in stage IE and four were in stage IIE. Three cases were treated with surgery alone and two cases with bulky inoperable stage IIB were treated with chemo-radiotherapy. Chemotherapy induced a complete response in one and a partial response in the other with minimal transient toxicity. As the questions regarding justification for extensive surgical intervention increase, combined chemo-radiotherapy can be suggested as an initial treatment even in stage I, and stage II thyroid lymphoma based on prognostic factor evaluation.

Aged↗
PubMed1995

[Complications of massive blood transfusion after intrathoracic hemorrhage--a case report].

Acute hemorrhage leading to acute hypovolomic shock is a medical emergency carrying high mortality. It therefore requires prompt and effective treatment. We reported a case of lung tumor receiving lobectomy at our hospital. Repeated internal bleeding due to subclavian artery perforation occurred three times within three weeks after the surgery. During the period of resuscitation, the patient received emergently massive blood transfusion. Some complications of massive blood transfusion. Some complications of massive blood transfusion were noted later. A total of 89 units of whole blood, 34 units of fresh frozen plasma and 28 units of platelet was given.

Aged↗
PubMed1994

Tumor growth and angiogenesis induced by a secreted binding protein for fibroblast growth factors.

Basic fibroblast growth factor (bFGF) is a strong inducer of angiogenesis and thus may play an important role in the growth of solid tumors. However, bFGF is usually found immobilized on the extracellular matrix, and it is only partly understood how it is solubilized to reach and activate its extracellular receptors. We studied the potential contribution to this process by a secreted binding protein (BP) with high affinity for FGFs. An expression vector for BP was transfected into a human cell line (SW-13) that contains constitutively high levels of bFGF. The BP-expressing cells began to grow colonies in soft agar due to their autocrine stimulation by bFGF and released biologically active bFGF into their media. Furthermore, they grew into well vascularized tumors in athymic nude mice. In addition, we found the BP mRNA expressed at high levels in squamous cell carcinoma (SCC) tissues from patients and in SCC cell lines of different origin as well as in immortalized keratinocytes. However, we failed to detect BP mRNA in normal adult tissues or in a number of non-SCC tumor cell lines. Expression of the secreted BP appears to be a mechanism through which immobilized FGF can be activated to support tumor growth and angiogenesis.

3T3 Cells↗
PubMed1994

Changing trends in histologic types of lung cancer during the last decade (1981-1990) in Korea: a hospital-based study.

A review of the histopathology and past history of 2229 patients with primary lung cancer diagnosed at the Yonsei University Medical Center from 1981 to 1990 was performed to investigate the changes in histologic types and the relationship to smoking history. The most frequent histologic type of lung cancer was squamous cell carcinoma (956 patients, 54.0%) followed by adenocarcinoma (311 patients, 17.6%) in males (1772 patients), and adenocarcinoma (206 patients, 45.1%) followed by squamous cell carcinoma (126 patients, 27.6%) in females (457 patients). In both sexes, the predominant type was adenocarcinoma under the age of 40, whereas squamous cell carcinoma was the most frequent type above the age of 40. While squamous cell carcinoma decreased over 10 years (54.3% in 1981, 44.3% in 1990), adenocarcinoma showed a gradually increased incidence (17.0% in 1981, 28.3% in 1990) in both sexes, and the proportion of small cell carcinoma and large cell carcinoma remained unchanged. These changes in histologic type were more prominent in non-smokers. In conclusion, the increasing incidence of adenocarcinoma in both sexes, especially in non-smokers, suggests the possible presence of etiologic factors other than smoking, such as environmental pollution.

Adolescent↗
PubMed1994

Purification and characterization of alkaline serine protease from an alkalophilic Streptomyces sp.

SAP, an extracellular alkaline serine protease produced by Streptomyces sp. YSA-130, was purified to homogeneity by CM-Sephadex column chromatography and crystallization. The enzyme was a monomeric protein with a molecular weight of 19,000 as estimated by SDS-PAGE and gel filtration. The amino acid composition and amino-terminal sequence of SAP were similar to those of other bacterial serine proteases, i.e., Streptomyces griseus proteases A and B, Lysobacter enzymogenes alpha-lytic protease and Nocardiopsis dassonvillei subsp. prasina OPC-210 alkaline serine protease NDP-I. The optimum temperature and pH for the enzyme activity were 60 degrees C and 11.5. The enzyme was stable up 50 degrees C, and between pHs 4 and 12. The activity was inhibited by Ag+, Hg2+, Co2+, sodium dodecyl sulfate. N-bromosuccinimide, diisopropyl phosphorofluoridate (DFP), 2,3-butanedione, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), iodoacetate, N-ethylmaleimide (NEM), phenylmethanesulfonyl fluoride (PMSF), and phenylglyoxal.

Amino Acid Sequence↗
PubMed1993

Effects of dietary fat source on sudden death syndrome and cardiac sarcoplasmic reticular calcium transport in broiler chickens.

Wheat and soybean diets supplemented with either tallow or sunflower oil (SFO) were fed to broiler chicks. Variables examined included performance, incidence of sudden death syndrome (SDS), and cardiac sarcoplasmic reticular (SR) calcium transport. The phospholipid content of heart tissues was also determined. Birds fed the SFO diet gained significantly (P < .05) more weight over the first 21 days of age and had a significantly better feed:gain ratio (P < .01). The incidence of SDS mortality up to 39 days of age was also lower (P < .05) for SFO-fed birds than for those fed the tallow diet. Calcium (45Ca2+) uptake and calcium-magnesium 5'-adenosinetriphosphatase (Ca2+ + Mg(2+)-ATPase) activity in cardiac SR vesicles did not differ due to diet (P > .05). However, compared with similar weight pen-mates showing no disease signs, SDS birds had depressed 45Ca2+ uptake (P < .01) and Ca2+ + Mg(2+)-ATPase (P < .05) of cardiac SR vesicles. The phosphatidylcholine concentration in the cell membranes of heart tissue of tallow-fed birds was significantly higher (P < .05) than in SFO-fed chicks. No differences were seen in other phospholipid constituents. The SDS birds, however, had significantly (P < .05) lower phosphatidylethanolamine plus phosphatidylglycerol, sphingomyelin, and total phospholipid concentrations in the heart tissues than the pen-mate controls. The results support the hypotheses that SDS in broilers is a cardiac dysfunction associated with defective cardiac SR membrane function and that dietary fat type is implicated with the syndrome.

Animals↗
PubMed1992

Phase II trial for combined external radiotherapy and hyperthermia for unresectable hepatoma.

Hepatocellular carcinoma is a major malignant disease in parts of Africa and Asia, including Korea. Surgical resection, which represents the best hope for cure, is limited by the extent of the disease and the high incidence of concurrent liver cirrhosis in Korea. We designed a phase II trial of combined external radiotherapy and hyperthermia for hepatocellular carcinoma that was unresectable due to either locally advanced lesions or associated liver cirrhosis so as to evaluate the efficacy and the safety of this combination regimen. This trial was performed at Yonsei Cancer Center between April 1988 and July 1988. External radiotherapy was delivered to a total dose of 3060 cGy/3.5 weeks. Hyperthermia was applied twice a week for a total of six treatment sessions using an 8-MHz radio-frequency capacitive-type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases, hyperthermia was carried out within 30 min of the radiotherapy for a period of 30-60 min. The temperature in the tumor was measured by inserting a thermocouple into the tumor mass under ultrasonographic guidance in patients who did not have a bleeding tendency. The tumor response was assessed by CT scan after completion of the designed treatment. No complete response was obtained. However, a symptomatic improvement in abdominal pain was observed in 78.6% of cases and a partial response was achieved in 40% of the patients. The most important factor affecting the tumor response was the type of tumor (single massive, 71.4%; diffuse infiltrative, 20%; multinodular, 0; P < 0.005). The 1-year survival values determined for all patients and for the partial responders were 34% and 50%, respectively. The overall median duration of survival was 6.5 months. The median duration of survival for the partial responders was longer than that for the nonresponders (11 vs 5 months; P < 0.05). A mild degree of heat sensation, fever, first-degree burns of the skin, and nausea were observed as treatment-related adverse reactions. In conclusion, although this study is being continued, the results obtained thus for indicate that combined radiotherapy and hyperthermia seem to be effective in providing local tumor control and pain palliation in unresectable hepatocellular carcinoma while producing an acceptable level of toxicity.

Adult↗
PubMed1992

Arachidonic acid regulates the phosphoinositide signal transduction pathway in submandibular acinar cells.

Modulation of the phosphoinositide signal transduction pathway by arachidonic acid (AA) in collagenase-dispersed rat submandibular acinar cells was investigated. The muscarinic agonist, carbachol, stimulated PIP2 hydrolysis and the generation of IP3 to five-fold the control levels. This response was inhibited by 75% on pre-treatment of cells with AA. The AA inhibitory effect was not duplicated by a range of prostaglandins and leukotrienes and was not reversed by blockers of the cyclo-oxygenase and lipoxygenase synthetic pathways, indicating that AA action was not mediated by eicosanoid metabolites. Additional experiments confirmed that the enzyme, protein kinase C, was also not a mediator of the AA effect. Arachidonic acid did not affect the uptake of radioactive inositol into acinar cells, but it did inhibit the incorporation of inositol into inositol phospholipids of the phosphoinositide cycle. In studies on inositol phospholipid turnover, AA alone reduced the level of PIP2 but not of PIP or PI. Under conditions of PI cycle stimulation with carbachol, AA significantly lowered PIP2 and PIP but not PI. These findings suggest that arachidonic acid may regulate the phosphoinositide response by inhibiting the synthetic phase of the cycle at a locus distal to PI generation.

Animals↗