Biomedical subjects

S H Yoon

Publications and source records attributed to S H Yoon.

At least 37 records · Page 2Linked to original sources

PubMed2001

Expression and regulation of phospholipase D during neuronal differentiation of PC12 cells.

To assess a possible role for phospholipase D (PLD) in PC12 cell signal transduction and differentiation, we have investigated the expression of PLD in PC12 cells and found that the differentiation factor, nerve growth factor (NGF) increased PLD1 protein expression and phorbol 12-myristate 13 acetate (PMA)-induced PLD activity. During neuronal differentiation, this effect showed correlation to the protein expression levels of classical protein kinase C (PKC) isozymes, PKC-alpha and -beta II, but there was no significant increase in the protein level of RhoA, another regulatory factor for PLD activation. Interestingly, PLD1 was associated with PKC-alpha or beta II, and its association gradually increased as NGF-induced neuronal differentiation progressed. PKC inhibitor, Ro-31-8220, caused a significant inhibition of neurite outgrowth and PLD activity. Furthermore, PLD1 was constitutively associated with the Shc adaptor molecule, the overexpression of which is known to induce PLD activity and to induce neurite outgrowth. Taken together, the data in this study suggests that PLD1 is closely implicated in neuronal differentiation of PC12 cells.

Amino Acid Sequence↗

PubMed2001

Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1.

The effects of fluoxetine and its major metabolite, norfluoxetine, were studied using the patch-clamp technique on the cloned neuronal rat K(+) channel Kv3.1, expressed in Chinese hamster ovary cells. In whole-cell recordings, fluoxetine and norfluoxetine inhibited Kv3.1 currents in a reversible concentration-dependent manner, with an IC(50) value and a Hill coefficient of 13.11+/-0.91 microM and 1.33+/-0.08 for fluoxetine and 0.80+/-0.06 microM and 1.65+/-0.08 for norfluoxetine at +40 mV, respectively. In inside-out patches, norfluoxetine applied to the cytoplasmic surface inhibited Kv3.1 with an IC(50) value of 0.19+/-0.01 microM. The inhibition of Kv3.1 currents by both drugs was characterized by an acceleration in the apparent rate of current decay, without modification of the activation time course and with relatively fewer effects on peak amplitude. The degree of inhibition of Kv3.1 by norfluoxetine was voltage-dependent. The inhibition increased steeply between 0 and +30 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +30 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.31+/-0.05. The association (k(+1)) and dissociation (k(-1)) rate constants for norfluoxetine-induced inhibition of Kv3.1 were 21.70+/-3.39 microM(-1) s(-1) and 14.68+/-3.94 s(-1), respectively. The theoretical K(D) value derived by k(-1)/k(+1) yielded 0.68 microM. Norfluoxetine did not affect the ion selectivity of Kv3.1. The reversal potential under control conditions was about -85 mV and was not affected by norfluoxetine. Norfluoxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of norfluoxetine, were superimposed. The voltage dependence of steady-state inactivation was not changed by the drug. Norfluoxetine produced use-dependent inhibition of Kv3.1 at a frequency of 1 Hz and slowed the recovery from inactivation. It is concluded that at clinically relevant concentrations, both fluoxetine and its major metabolite norfluoxetine inhibit Kv3.1, and that norfluoxetine directly inhibits Kv3.1 as an open channel blocker.

Algorithms↗

PubMed2001

Flux enhancement with gas injection in crossflow ultrafiltration of oily wastewater.

The gas injection technique was introduced to achieve flux improvement in cross-flow ultrafiltration of oil emulsion. By the nitrogen gas injection, homogeneous liquid phase oil/water emulsion was changed to heterogeneous gas- liquid phase. The injected gas causes positive effect of promoting turbulence, but it also has negative effect of decreasing the effective membrane area due to the partial occupation of membrane pores by bubbles. The efficiency of the gas injection was found out to be dependent on bubble fractions in the mixture: at sufficient bubble fractions the higher flux was observed. but at lower bubble fractions the flux rather decreased compared with that without gas injection. An attempt was made to explain the mechanisms for the dual aspects of gas injection. Turbulence dampening effect was also observed when the dependence of mass transfer coefficient on cross-flow rate was investigated with gas injection.

Air Movements↗

PubMed2001

Effects of temperature and agitation rate on the formation of conjugated linoleic acids in soybean oil during hydrogenation process.

The effects of hydrogen temperature and agitation rate on the formation of total conjugated linoleic acids (CLA) and CLA isomers were studied during hydrogenation with a selective Ni catalyst. The CLA isomers were identified by using a 100-m cyano-capillary column gas chromatograph and a silver ion-impregnated HPLC. Reaction temperature and agitation rate greatly affected the quantities of total CLA and individual CLA isomers, and the time to reach the maximum quantity of CLA in the partially hydrogenated soybean oil. As the hydrogenation temperature increased, the maximum quantity of CLA in soybean oil increased, but the time to reach the maximum CLA content decreased. By increasing the hydrogenation temperature from 170 to 210 degrees C, the quantity of CLA obtained was about 2.6 times higher. As the agitation rate decreased, the CLA formation in soybean oil increased, and the time to reach the maximum CLA content also increased. The maximum CLA contents in soybean oil obtained during hydrogenation at 210 degrees C with agitation rates of 300, 500, and 700 rpm were 162.82, 108.62, and 66.15 mg total CLA/g oil, respectively. The present data showed that it is possible to produce high-CLA-content soybean oil without major modification of fatty acid composition by short-time (10 min) selective hydrogenation under high temperature and low agitation rate conditions.

Chromatography, Gas↗

PubMed2001

Pregnancies resulting from in vitro matured oocytes collected from women with regular menstrual cycle.

PURPOSE: To demonstrate that human immature oocytes retrieved from women with regular menstrual cycles can undergo maturation and fertilization, and that the resulting embryos can establish pregnancies. METHODS: Immature oocytes (n = 568) were retrieved from women with regular menstrual cycle. The intact immature oocytes (n = 506) were allowed to mature in YS medium supplemented with 70% human follicular fluid (hFF); the matured oocytes were fertilized with husband sperm. Two pronuclei oocytes were cocultured with cumulus cells in YS medium supplemented with 10% hFF until 2 or 3 days after insemination. The cleaved embryos were transferred in uteri. RESULTS: Follicles were aspirated on Day 9.2 +/- 5.3 of 63 natural cycles from 51 patients (mean age = 34.8 +/- 4.0 years). The average number of retrieved immature oocytes was 9.0. The maturation rate was 74.3% (376/506). The two PN and cleavage rates were 72.6% (273/376) and 89.0% (243/273), respectively. Embryo transfer was achieved in 51 cycles and clinical pregnancy rate was 17.6% (9/51). CONCLUSIONS: The results suggest that in vitro matured oocytes can undergo fertilization and the resulting embryos may successfully lead to pregnancies. However, further research is needed to improve IVM technique to achieve success rate comparable to gonadotrophin stimulated cycles.

Adult↗

PubMed2001

Alternative embryo transfer on day 3 or day 5 for reducing the risk of multiple gestations.

PURPOSE: This study was carried out to reduce the possibility of high-order multiple gestations and the failure of embryo transfer by determining their replacement date based on the number and quality of 2-day embryos. METHODS: All zygotes were cocultured with cumulus cells in 10 microliters of YS medium containing 10% human follicular fluid (hFF) for 48 or 96 hr. In period I, all embryos were transferred on day 3 (1032 cycles). In period II, the embryos were transferred on either day 3 or day 5 by determining their replacement date based on the number and quality of 2-day embryos: there were 2701 patients in whom embryos were replaced on day 3 (in the case that the number of zygotes was less than eight and the number of good-quality embryos was less than three) and 1952 patients less than 40 years old in whom embryos were replaced on day 5 (in the case that the number of zygotes was eight or more and/or the number of good-quality embryos was three or more). On the other hand, patients who were 40 years old or more were alloted to day 3 transfer cycles, regardless of the number and quality of the 2-day embryos, due to the possibility of their not producing blastocyst-stage embryos in vitro. RESULTS: The number of embryos transferred in period II was 2.9 +/- 0.6, while that in period I was 3.7 +/- 0.5. The multiple pregnancy rate was significantly decreased in period II (30.7%) compared to that (49.6%) in period I, while the pregnancy and implantation rates in period II (36.1 and 16.4%, respectively) were not lower than those (34.9 and 16.1%, respectively) in period I. The rate of triplet or more gestations was significantly minimized in period II (2.3%) compared to that in period I (26.5%). CONCLUSIONS: We propose that determination of the date on which embryos should be transferred based on the number and quality of embryos on day 2 may help to maintain an acceptable pregnancy rate, while minimizing embryo transfer failure and high-order multiple gestations.

Adult↗

PubMed2001

A comparison of bowel care patterns in patients with spinal cord injury: upper motor neuron bowel vs lower motor neuron bowel.

STUDY DESIGN: A face-to-face interview survey. OBJECTIVE: To compare bowel care patterns in spinal cord injury (SCI) patients based on type of neurogenic bowel. SETTING: Department of Physical Medicine and Rehabilitation of a tertiary university hospital in Suwon, Korea. METHODS: Among chronic SCI patients, 22 patients with upper motor neuron bowel (UMNB) and 20 patients with lower motor neuron bowel (LMNB) participated in an interview survey for the evaluation of bowel care patterns. RESULTS: The patients with LMNB demonstrated increased frequency of defecation, increased frequency of fecal incontinence, increased use of oral medications for bowel care, increased required time for defecation and more diet modification than those with UMNB (P < 0.05). However, there was no significant difference in the subjective difficulty of bowel care. Among several available bowel care methods, suppositories were used most frequently by the UMNB group, whereas the Valsalva maneuver was the most frequently used method by the LMNB group. CONCLUSIONS: Patients with LMNB tend to suffer more difficulties in management of their neurogenic bowel than those with UMNB. Therefore, more intensive and aggressive bowel care programs should be provided for SCI patients with LMNB.

Activities of Daily Living↗

PubMed2001

Improvement of tagatose conversion rate by genetic evolution of thermostable galactose isomerase.

To enhance the isomerization rate of galactose into tagatose, a thermostable galactose isomerase, which was isolated from bacteria growing in a hot spring, was genetically improved using the error-prone PCR method. From 500 mutant clones, a clone showing improved conversion activity was selected. The sequence of the selected clone had five amino acid changes: His(228)-->Asp, Gly(384)-->Asp, Ser(393)-->Thr, Lys(428)-->Asn and Asp(475)-->Lys. The improved galactose isomerase had an 11-fold higher reaction rate than the original.

Aldose-Ketose Isomerases↗

PubMed2001

Involvement of cyclic GMP in nitric-oxide-induced gastric relaxation Comparison of the actions of cyclic GMP and cyclic AMP.

BACKGROUND: Smooth muscle relaxation induced by various agents that increase the cellular levels of cyclic nucleotides (cAMP and cGMP) is accompanied by a decrease in intracellular Ca2+ concentration. However, little is known about the differences between the inhibitory effects of cAMP and cGMP on the contraction of smooth muscle. OBJECTIVE: To compare the effects and underlying mechanisms of cAMP and cGMP on the inhibition of gastric smooth muscle contraction, cyclic nucleotide promoting agents, as well as cell membrane permeable cyclic nucleotides were used. METHODS: Isometric contraction was measured from circular muscle strips prepared from the fundus of cat stomach in a cylinder-shaped chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 degrees C) bubbled with 5% CO2 in O2. The level of inositol phosphates (IPs) was measured. RESULTS: Forskolin and sodium nitroprusside significantly inhibited acetylcholine (ACh)-induced gastric smooth muscle contraction and increased the cellular levels of cAMP and cGMP, respectively. Direct application of 8-Br-cAMP and 8-Br-cGMP also significantly inhibited ACh-induced contraction. Both verapamil and TMB-8 inhibited ACh-induced contraction. The combined inhibitory effect of verapamil and TMB-8 was significantly greater than the effect of either one, separately. Forskolin or sodium nitroprusside similarly augmented the effect of verapamil. However, the inhibitory effect of TMB-8 was augmented only by 8-Br-cGMP or sodium nitroprusside but not by 8-BrcAMP or forskolin. Forskolin and 8-Br-cAMP significantly inhibited the formation of inositol phosphates stimulated by ACh. CONCLUSIONS: cAMP inhibits the contraction mechanism associated with intracellular Ca2+ mobilization as well as extracellular Ca2+ influx, while cGMP inhibits contraction by inhibiting the mechanism associated with extracellular Ca2+ influx.

Acetylcholine↗

PubMed2001

Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts.

Phospholipase D (PLD) has been suggested to play an important role in a variety of cellular functions. PLD activity has been shown to be significantly elevated in many tumours and transformed cells, suggesting the possibility that PLD might be involved in tumorigenesis. In this study, we have established stable cell lines overexpressing PLD1 and PLD2 from fibroblast cells. These cells, but not control cells, showed altered growth properties and anchorage-independent growth in soft agar. Both PLD1 and PLD2 also induced an up-regulation of the activity of matrix metalloprotease-9 as detected by zymograms. Furthermore, both PLD1 and PLD2 transformants, but not vector-transfectants, induced undifferentiated sarcoma when transplanted into nude mice. Both PLD1- and PLD2-mediated cell cycle distributions in stable cell lines revealed an increased fraction of cells in the S phase compared with control cells. Interestingly, the level of cyclin D3 protein, known as an activator of G(1) to S phase transition in the cell cycle, was aberrantly high in cells overexpressing PLD1 and PLD2 compared with control cells. These results suggest that overexpression of PLD isozymes may play an important role in neoplastic transformation.

Animals↗

PubMed2001

Distributional patterns of phospholipase C isozymes in rat pancreas.

Phospholipase C (PLC) isozymes are believed to play a role in regulating pancreatic exocrine and endocrine secretion. In an attempt to investigate the role of PLC, we examined the distribution patterns of PLC isozymes in the normal rat pancreas by Western blot analysis and immunohistochemistry. Western blot analysis was performed on pancreatic acinar tissues and the islet of Langerhans, which were separated from each other. PLC-beta isozymes (beta1, beta2, beta3, and beta4), delta1, and delta2 were detected in both acinar and islet cells, whereas PLC-gamma1 and gamma2 were observed only in acinar tissues. On immunohistochemistry, the immunoreactivities of PLC isozymes except for PLC-gamma1 were observed as follows: PLC-beta1, in both the exocrine and endocrine tissues; PLC-beta2, mainly in the periphery of the islet and acinar cells; PLC-beta3, in the periphery of the islet and in some ductal epithelium; PLC-beta4, through the islet of Langerhans and ductal epithelium; PLC-gamma1, not detected in pancreatic tissue; PLC-gamma2, mainly in acinar cells; PLC-delta1 and delta2, in the islet and in ductal epithelium. These results suggest that the intrapancreatic site-specific existence of PLC isozymes may modulate pancreatic exocrine and endocrine functions through a PLC-mediated signal transduction.

Animals↗

PubMed2001

Effect of somatostatin on cholecystokinin-induced amylase release in rat pancreatic acini.

The effect of somatostatin on cholecystokinin-induced amylase release was investigated in isolated rat pancreatic acini. Acini were isolated by enzymatic digestion and incubated in a HEPES buffered Ringer's solution with testing reagents for 30 minutes at 37 degrees C. The activity of released amylase, cAMP, and inositol phosphate formation were measured. Intracellular calcium concentration ([Ca2+]i) was also checked. Somatostatin 14 and octreotide, a somatostatin analog, inhibited CCK-stimulated amylase release in a concentration-dependent manner. The inhibitory effect of octreotide on CCK-induced amylase release was not shown when the acini were treated with 8-Br-cAMP, irrespective of the presence of IBMX. Forskolin potentiated CCK-induced amylase release and this effect was blocked by octreotide treatment; although CCK-8 (3 x 10(-11) M) failed to stimulate cAMP formation, octreotide significantly inhibited basal cAMP formation in the acini. The increase of [Ca2+]i in response to CCK was inhibited by octreotide. However, CCK-induced inositol phosphate formation was not changed by 10(-9) M octreotide. Octreotide had no effect on CCK-stimulated tyrosine phosphorylation, and tyrosine phosphatase inhibitors (NaF and Na2WO4) did not influence the effect of octreotide on CCK-induced amylase release. From these results, we conclude that octreotide inhibits CCK-induced amylase release by inhibiting basal cAMP formation and decreasing the [Ca2+]i stimulated by CCK.

1-Methyl-3-isobutylxanthine↗

PubMed2001

Site-specific localization of protein kinase C isoforms in rat pancreas.

BACKGROUND: Protein kinase C (PKC), a major signal-transducing enzyme, is recognized to play an important role in the regulation of pancreatic exocrine and endocrine secretion, and yet the distribution of PKC isoforms in rat pancreas has remained unclarified. AIM OF THE STUDY: We examined the precise localization of PKC isoforms to elucidate the role of PKC in the normal rat pancreas. METHODS: Male Sprague-Dawley rats were used throughout the experiment. For Western blot analysis, the islet of Langerhans and the acinar tissue were separated by the collagenase digestion method. Also, the whole pancreas was taken out and immunohistochemistry performed. RESULTS: According to Western blot analysis, PKC-alpha, -gamma, -delta, -epsilon, -zeta, and -lambda were detected in both acinar and islet cells while PKC-beta II were observed exclusively in the islet. PKC-beta I was not observed. On immunohistochemistry, the immunoreactivities of PKC isoforms were observed as follows: PKC-alpha, weakly in some endocrine cells and ductal epithelium; PKC-beta II, mainly in the islet center; PKC-gamma, in the islet, intrapancreatic ganglia and ductal epithelium; PKC-delta, in the islet periphery, weakly in some acinar cells and ductal epithelium; PKC-epsilon, strongly in the islet, acinar cell and ductal epithelium; PKC-zeta, in the islet, acinar cell and ductal epithelium; PKC-lambda in some endocrine cells and ductal epithelium. CONCLUSION: These results suggest that the intrapancreatic site-specific existence of PKC isoforms may regulate pancreatic exocrine and endocrine functions via a PKC-mediated signal transduction.

Animals↗

PubMed2000

Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1.

We tested the cytotoxic action of 8-hydroxyguanine (8ohG) by observing the viability of several leukemic cell lines (KG-1, U937, Jurkat and K 562) in the presence of 8-hydroxydeoxyguanosine (8ohdG), a nucleoside of 8ohG. It was found that 8ohdG showed cytotoxic action only to KG-1 and that only KG-1 showed a homozygous arginine 209 to glutamine mutation in the hOGG1 gene with an almost negligible hOGG1 enzyme activity. Possibly, the selective cytotoxicity in 8ohdG to KG-1 may be due to its low capacity to cope with an increase in the 8ohG level in DNA resulting from the incorporation of 8ohdG present in the culture media. The mutational impairment of hOGG1 in KG-1 is the first report in leukemic cell lines. Using KG-1 with impaired hOGG1, we demonstrated cytotoxicity of 8ohdG probably due to its incorporation into cellular DNA. This new property of KG-1 may allow it to serve as an useful tool for studies of OGG1, oxidative DNA damage and the cytotoxic action of 8ohG. Oncogene (2000) 19, 4476 - 4479.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Soft drugs. 12. Design, synthesis, and evaluation of soft bufuralol analogues.

In the search for more potent but still short-acting beta-blockers (BB), the methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, 2-(1-adamantyl)ethyl, and methylthiomethyl esters of the acidic inactive metabolite of bufuralol were synthesized based on the "inactive metabolite" approach. The cleavage of the ester bond by blood and tissue esterases rapidly deactivates these compounds, resulting in an ultrashort duration of action. The beta-antagonist potencies and time courses of actions of the new "soft" BBs were characterized by recording ECG and intra-arterial blood pressure (BP) in rats. In the isoproterenol-induced tachycardia model, while bufuralol at an iv dose of 1 mg/kg (3.8 micromol/kg) diminished heart rate (HR) for at least 2 h, the effects of the soft drugs lasted for only 10-30 min at equimolar dose. The inactive metabolite did not decrease HR significantly. The first four members of this series of compounds showed the highest beta-blocking potencies, ranging between 25% and 50% of that of bufuralol. Next, the effects of these most active compounds on resting HR and BP were evaluated in comparison to esmolol. Infused for 10 min at a rate of 20 micromol/kg/min, esmolol decreased HR and mean arterial pressure (MAP) by 40% and 60%, respectively. The soft drugs at doses ranging only between 2 and 4 micromol/kg/min resulted in a 20-40% decrease in HR and a 30-50% reduction in MAP. However, the time courses of both the bradycardic and hypotensive effects of the soft drugs were superimposable to that of esmolol, diminishing within 60 min after the discontinuation of the infusions.

Adrenergic beta-Antagonists↗

PubMed2000

Reversal of hypercapnia induces KATP channel and NO-independent constriction of basilar artery in rabbits with acute metabolic alkalosis.

The mechanism of hypocapnic constriction of the cerebral vasculature under conditions of altered acid-base balance has not been investigated. As K(ATP) channels and NO have been implicated in hypocapnic constriction, this study investigated their roles in the constriction due to lowered pCO(2) in hypercapnic rabbits with acute metabolic alkalosis. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Lowering blood pCO(2) from initial baseline hypercapnic levels to near normocapnic and hypocapnic levels constricted basilar artery by 10.2+/-0.8% (4) and 16.2+/-0.6% (44), respectively (means+/-S.E., n), as determined in an in situ cranial window preparation. The constrictions were maintained for 4-5 h and return of pCO(2) to hypercapnic levels relaxed the constriction. Changing the suffusate pH to either the pH of the cerebral spinal fluid observed during initial baseline hypercapnia or following lowered pCO(2) did not alter the magnitude of constriction due to lowered pCO(2). Neither 0.3 mM N(G)-monomethyl-L-arginine monoacetate, an NO synthase inhibitor, nor 10 microM glibenclamide, a K(ATP) channel blocker, altered the magnitude of hypocapnic constriction. These results demonstrated that under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent pCO(2) reduction induces prolonged constriction of the basilar artery that is independent of (1) cerebral spinal fluid pH over a physiologic range, and (2) NO and K(ATP) channels.

ATP-Binding Cassette Transporters↗

PubMed2000

Reversal of hypercapnia induces endothelin-dependent constriction of basilar artery in rabbits with acute metabolic alkalosis.

We recently concluded that constriction of basilar artery due to respiration-induced hypocapnia in rabbits with acute metabolic alkalosis and accompanying compensatory hypercapnia was independent of NO and K(ATP) channels. Based on reports that endothelin-1-mediated hypocapnic constriction of the rabbit basilar artery in vitro, we further investigated whether the respiration-induced hypocapnic constriction was endothelin-1 mediated. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. The ET(A) plus ET(B) receptor antagonist, PD145065 (1 microM), and the selective ET(A) receptor antagonist, BQ610 (3 microM), completely relaxed the hypocapnic constriction, as determined in a cranial window. Unexpectedly, the ET(B) receptor antagonists, BQ788 and RES-701-1 (3 microM), relaxed the constriction by 72.1+/-2.8% (4) and 77.2+/-8.7% (5), respectively (means+/-S.E. (n)). To investigate whether the large magnitudes of relaxation to both ET(A) and ET(B) receptor antagonists were due to nonselectivity of the antagonists, the effects of the antagonists on the constriction to exogenous endothelin-1 were evaluated. BQ610, BQ788, and RES-701-1 relaxed the 3-5 nM endothelin-1 constriction by only 64.3+/-7.6% (4), 43.5+/-8.5% (5), and 26.7+/-4.8% (3) (means+/-S.E. (n)), respectively, consistent with the selective blocking action of these antagonists. To investigate whether the greater magnitude of BQ610, BQ788, and RES-701-1 relaxation of hypocapnic constricted versus exogenous endothelin-1-constricted vessels was due to differences between constriction elicited by endogenous versus exogenous endothelin-1, the effects of the endothelin receptor antagonists on constriction to isocapnic alkaline suffusate were evaluated. PD145065 (1 microM) and 0.1 mM phosphoramidon, an endothelin-converting enzyme inhibitor, inhibited the constriction to isocapnic alkaline suffusate by 83.8+/-7.8% (6) and 74.3+/-9.7% (8) (means+/-S.E. (n)), respectively, consistent with the endothelin-1 dependency of the constriction. BQ610, BQ788, and RES-701-1 relaxed the isocapnic alkaline suffusate constriction by 74.9+/-6.7% (5), 65.5+/-6.4% (5), and 78.0+/-6.5% (4) (means+/-S.E. (n)), respectively. Thus, the relaxation profile to the selective endothelin receptor antagonists in isocapnic alkaline constricted vessels more closely approximated the relaxation profile observed in hypocapnic constricted as compared to endothelin-1-constricted vessels. Hypocapnia did not alter the 5 nM endothelin-1 constriction. These results suggest that, under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent hypocapnic constriction is endothelin mediated. Both ET(A) and ET(B) receptor activation may mediate the hypocapnic constriction. The hypocapnic constriction is not due to enhanced endothelin-1 constriction and, thus, is due to the release of endothelin-1 and/or additional endothelins.

Alkalosis↗

PubMed2000

Brain-targeted chemical delivery of [Leu2, Pip3]-TRH: synthesis and biological evaluation.

A chemical targeting system for [Leu2, Pip3]-TRH (Gln,Leu,Pip) was synthesized in order to allow its specific delivery to the central nervous system (CNS). Sequential metabolism of the obtained 'packaged' chemical delivery system, (CDS), DHT-Pro-Pro-Gln-Leu-Pip-OCh, should yield a 'locked-in' precursor following the oxidative conversion of the dihydrotrigonellyl (DHT) to the trigonellyl (T+) moiety, followed by removal of the cholesteryl function and cleavage of the T+-Pro-Pro by prolyl endopeptidase. The antagonism of barbiturate-induced sleeping time was used to assess the activity of the CDS. The sleeping time after administration of vehicle and [Leu2]-TRH was 100.5 +/- 6.3 min, and 78.2 +/- 4.7 min, respectively. The [Leu2, Pip3]-TRH-CDS showed a significant decrease in sleeping time (58.2 +/- 3.4 min) compared to the vehicle or [Leu2]-TRH. These results indicate successful brain delivery of the precursor construct, and an effective release of the active GlnLeuPip in the brain.

Amino Acid Sequence↗