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K Horie

Publications and source records attributed to K Horie.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effect of receptor density on the receptor-effector coupling: use of cloned and stably expressed alpha 1B-adrenoceptors in CHO cells.

Using Chinese hamster ovary cells stably expressing alpha 1B-adrenoceptor as a model, we investigated whether the changes in receptor density may influence the receptor-effector coupling relationship. Among the transfected cells, two clones which showed similar pharmacological properties but markedly differed in receptor density (Bmax were 1600 and 110,000 sites/cell, respectively), were examined. The phenoxybenzamine inactivation method showed that the alpha 1B-adrenoceptor occupancy and transients of cytosolic Ca2+ concentration ([Ca2+]i) response relationship was markedly nonlinear but similar in the two cell lines. The dose-response relationship for norepinephrine-induced [Ca2+]i response showed an increase in maximum effect with no change in agonist potency, and the increase in maximum effect was disproportionate to the difference in receptor density. The results indicate that the classical model of drug-receptor action cannot appropriately describe the coupling of alpha 1B-adrenoceptor to [Ca2+]i response in the single receptor expressing system.

Animals↗
PubMed1995

Use of recombinant alpha 1-adrenoceptors to characterize subtype selectivity of drugs for the treatment of prostatic hypertrophy.

Several alpha 1-adrenoceptor antagonists have recently been developed for the treatment of benign prostatic hypertrophy because of their less frequent systemic side-effects compared to conventional alpha 1-adrenoceptor blockers. One potential explanation for their good tolerability would be the selectivity for a certain subtype of alpha 1-adrenoceptor. Utilizing COS-7 cells expressing the rat alpha 1A, the hamster alpha 1B and the human alpha 1C-adrenoceptors, we investigated affinities of alfuzosin, doxazosin, terazosin, indoramin and (+)- and (-)-5-[2-[[2-(o-ethoxyphenoxy)ethyl] amino]propyl]-2-methoxybenzesulfonamide HCl (YM 617) compared to prazosin. Radioligand binding studies showed that the affinities of alpha 1-adrenoceptor subtypes for alfuzosin (Ki value; alpha 1A: 2.4 nM, alpha 1B:1.4 nM, alpha 1C:4.2 nM), doxazosin (Ki value; alpha 1A:2.7 nM, alpha 1B:3.2 nM, alpha 1C:7.5 nM), terazosin (Ki value; alpha 1A:2.5 nM, alpha 1B:2.7 nM, alpha 1C:7.1 nM), indoramin (Ki value; alpha 1A:69 nM, alpha 1B:21 nM, alpha 1C:13 nM) and prazosin (Ki value; alpha 1A:0.16 nM, alpha 1B:0.19 nM, alpha 1C:0.2 nM) were equipotent to the three receptor subtypes. Unlike these antagonists, both (+)- and (-)-YM617 had relatively lower affinity for alpha 1B receptors compared to the other subtypes (Ki value; for (+)-YM617, alpha 1A:22 nM, alpha 1B:96 nM, alpha 1C:4.3 nM; for (-)-YM617, alpha 1A:0.11 nM, alpha 1B:0.7 nM, alpha 1C:0.035 nM). The data suggest that alpha 1-adrenoceptor antagonists currently used for the treatment of the benign prostatic hyperplasia do not show substantial subtype selectivity.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

Effects of a structural change in collagen upon binding to conditioned dentin studied by 13C NMR.

To develop a better adhesive functional monomer, it is imperative to understand the adhesion mechanisms of the resin to the dentin surface. Bond strength to the decalcified dentin surface pretreated with dentin primer, an aqueous ethanol solution of N-methacryloyl glycine, increases by increasing the water content in the primer. The aqueous primer could increase the thickness of the hybrid layer. The structural change of dentinal collagen with NM alpha A was studied by using a model compound for collagen,--(1Pro-2Pro-3Gly)10--, by 13C nuclear magnetic resonance (NMR). The model compound was aggregated in ethanol but dissociated in water. It was found that NM alpha A effectively dissociated the aggregated model compound in water. The dissociation of decalcified dentin was essential to create a thick hybrid layer that could afford a higher bond strength to dentin.

Adhesiveness↗
PubMed1995

Endothelin-1 and endothelin-3 modulate dopaminergic neurons through different mechanisms.

Novel vasoconstrictor peptides, endothelin-1 (ET-1) and endothelin-3 (ET-3), are also known as neuropeptides or neuromodulators. When either ET-1 or ET-3 was administered to the rat striatum via a microinjection needle, the dopamine release from the striatum dose-dependently increased. Pretreatment with a glutamate receptor blocker, glutamate diethyl ester hydrochloride, inhibited the dopamine release induced by ET-3, whereas it further enhanced the dopamine release by ET-1. This suggests that ET-1 directly induces the dopamine release, whereas the action of ET-3 is mediated by glutamate receptors. We postulate that this difference may result from the different distributions of endothelin receptors: ETA receptors may be present on the dopaminergic neurons, but ETB receptors on the glutamatergic neurons.

Animals↗
PubMed1995

Adhesion of composite to polished dentin retaining its smear layer.

OBJECTIVES: This study was designed to measure the adhesion of a composite to the smear layer. METHODS: An experimental aqueous bonding agent was supplied in the form of two liquids. One contained methacryloyl tyrosine amide (MTYA), glyceryl methacrylate (GM), dimethylaminoethylmethacrylate and benzene sulfinic acid sodium salt, and the other contained glutaraldehyde, succinic acid and 2-hydroxy-3-(3,4-dimethyl-9-oxo-9H-thioxanthen-2-yloxy)-N,N, N-trimethy-1-propanaminium chloride (QTX). QTX is a unique water-soluble photo polymerization initiator. The application times and irradiation times of the experimental aqueous bonding agent were varied. RESULTS: The highest mean bond tensile strength was obtained by irradiating the bonding agent for 1 min. A 3 min irradiation decreased the mean bond strength when the bonding agent was applied to the polished dentin surface for 1, 3 or 5 min. The mean values resulting from the application of experimental aqueous bonding agent were higher than those from a commercially available bonding agent which preserved or modified the smear layer. There was a significant decrease in the bond strength after 500 or 2000 thermocycles in specimens with a 5 min application of the bonding agent, but there was no significant decrease in the bond strength when the application time was for 1 or 3 min. SEM observation showed the formation of a hybrid layer with a thickness of approximately 1-1.5 micrometers. SIGNIFICANCE: The aqueous bonding agent tested in this investigation was capable of penetrating the smear layer and the bond strength exceeded the values obtained by bonding agents that remove the smear layer.

Analysis of Variance↗
PubMed1995

In vitro and in vivo effects of somatostatin on the growth of A431 cells.

We previously reported that the octapeptide somatostatin (SS) analogue SMS 201-995 (SMS) unexpectedly stimulates the growth of A431 human epidermoid carcinoma cells in vitro. In the present study, we found that both SS-14 and SS-28 also stimulated the growth of A431 cells in vitro. The proliferative effect of SS-28 also stimulated the growth of A431 cells in vitro. The proliferative effect of SS-28 was greater than that of SS-14. In contrast, there was no difference in A431 cell tumor weight or area between the SMS-treated or untreated athymic, tumor-bearing mice. The serum epidermal growth factor (EGF) level of the SMS-treated mice was significantly lower than that of the untreated mice. Decreases in serum EGF may attenuate the proliferative effect of SMS in vivo.

Animals↗
PubMed1995

Purification and characterization of thrombopoietin.

A thrombopoietic factor, termed thrombopoietin (TPO), was highly purified directly from the plasma of sublethally irradiated 1,100 rats by measuring the production of megakaryocytes from a highly enriched population of rat megakaryocyte progenitor cells (CFU-MK). The rat plasma TPO is a glycoprotein and strongly hydrophobic. The total activity and purification yields obtained were about 29% and 1.49 x 10(8), respectively. The amino acid sequences of the two peptide fragments prepared from the purified 19 kDa TPO were analyzed, and used for the cloning of rat and human TPO cDNAs. It was found that the 19 kDa TPO was truncated but comprised at least 163 amino acids. The sequence of human TPO cDNA revealed that the TPO was identical to the c-Mpl ligand. Both rat and human TPOs expressed in COS-1 cells exhibited significant activity toward the CFU-MK in vitro, and were active in stimulating platelet production in mice. These results indicate that a thrombopoietic factor originally found in the irradiated rat plasma is a ligand for the rat c-Mpl.

Amino Acid Sequence↗
PubMed1995

The role of IL-4 and IL-6 in IL-1-dependent cartilage matrix degradation.

The objective of this paper was to study the effects of interleukin 4 (IL-4) and interleukin 6 (IL-6) on cartilage matrix degradation, the production of chondroitin-4-sulphate (C4S) and chondroitin-6-sulphate (C6S), metalloproteinase (stromelysin 1 = MMP-3) and metalloproteinase inhibitor (TIMP-1) production. Cartilage matrix degradation was assayed the release of 35SO4 from chondrocyte cultures. TIMP-1 and MMP-3 were measured by ELISA. C6S and C4S were measured by HPLC analysis. IL-1 beta significantly enhanced C4S production and significantly suppressed C6S production. Thus, the C4S/C6S ratio was significantly enhanced by IL-1 beta, and significantly suppressed by IL-4. IL-4 removed the suppressing effects of IL-1 beta for C6S and the enhancing effects of IL-1 beta for the C4S/C6S ratio. Whereas IL-1 beta stimulated the production of MMP-3, IL-4 and IL-6 had no effect on enzyme activity. IL-4, but not IL-6, removed the enhancing effects of IL-1 beta for MMP-3. In contrast, IL-4 and IL-6 significantly enhanced TIMP-1 production in chondrocytes, IL-4, but not IL-6, also significantly suppressed IL-1 beta-mediated cartilage matrix degradation. On the other hand, IL-6 significantly suppressed spontaneous cartilage matrix degradation which is supposed to be mediated by the autocrine IL-1 mechanisms. In conclusion our results suggest that IL-4 and IL-6 both protect the cartilage matrix degradation induced by IL-1.

Bone Matrix↗
PubMed1995

The potential of oral mucosal cells for cultured epithelium: a preliminary report.

We have developed a method to fabricate cultured epithelium for skin repair using mucosal cells. We grafted this epithelium in six cases. The site where the mucosal epithelium was transplanted keratinized normally within 4 weeks and formed normal skin. Mucosal epithelial cells have many advantages over skin epidermal keratinocytes: (1) Mucosal epithelial cells grow faster than skin keratinocytes. (2) Cultured epithelial sheets formed using mucosal cells remain viable for at least 14 days in vitro. (3) The oral cavity is a suitable location to take a tissue segment because scar due to biopsy is inconspicuous. Therefore, mucosal epithelial cells are a potential new source of cells for cultured epithelial graft.

Adult↗
PubMed1995

Selectivity of the imidazoline alpha-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned alpha 1-adrenoceptor subtypes.

1. To investigate the structure-activity relationships of alpha-adrenoceptor agonists for the alpha 1-adrenoceptor subtypes, we have compared the imidazoline class of compounds, oxymetazoline and cirazoline, with the phenethylamine, noradrenaline, in their affinities and also in their intrinsic activities in Chinese hamster ovary (CHO) cells stably expressing the cloned human alpha 1-adrenoceptor subtypes (alpha 1a-, alpha 1b-, and alpha 1d-subtypes). 2. Radioligand binding studies with [125I]-HEAT showed that cirazoline and oxymetazoline had higher affinities at alpha 1a-subtype than at alpha 1b- and alpha 1d-subtypes, while noradrenaline had higher affinity at the alpha 1d-subtype than at alpha 1a- and alpha 1b-subtypes. 3. In functional studies, cirazoline caused transients of cytosolic Ca2+ concentrations ([Ca2+]i response) in a concentration-dependent manner and developed a maximal response similar to that to noradrenaline in CHO cells expressing the alpha 1a-subtype, while it acted as a partial agonist at alpha 1b- and alpha 1d-adrenoceptors. Oxymetazoline, on the other hand, was a weak agonist at alpha 1a-adrenoceptors, and has no intrinsic activity at the other subtypes. 4. Using the phenoxybenzamine inactivation method, the relationships between receptor occupancy and noradrenaline-induced [Ca2+]i response for alpha 1a- and alpha 1d-subtypes were found to be linear, whereas it was moderately hyperbolic for the alpha 1b-subtype, indicating the absence of receptor reserves in CHO cells expressing alpha 1a- and alpha 1d-subtypes while there exists a small receptor reserve for CHO cells expressing the alpha 1b-subtype. 5 In summary, our data obtained in cells exclusively expressing a single receptor subtype support the idea that the relative role of agonist affinity and intrinsic activity may vary depending on the subtype of alphal-adrenoceptor.

Adrenergic alpha-Agonists↗
PubMed1995

Modulation of angiotensin II type 1 receptor mRNA expression in human blood cells: comparison of platelets and mononuclear leucocytes.

The objective of the present study was to quantify the expression of angiotensin II type 1 (AT1) receptor transcripts in human blood cells--platelets and mononuclear leukocytes--from 10 normal healthy volunteers during the alterations in the renin-angiotensin system. A quantitative assay employing reverse transcription-polymerase chain reaction (RT-PCR) was utilized. Oral administration of furosemide, 40 mg for 2 days, under mild salt restriction (50 mEq NaCl/day) for 6 days stimulated the renin-angiotensin system resulting in significant increases in plasma renin activity (PRA) (1.84 +/- 0.12 vs. 1.05 +/- 0.17 ng/l/s; P < 0.01), plasma angiotensin II concentration, and plasma aldosterone concentration (PAC). The ratio of AT1 receptor mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in mononuclear leucocytes was significantly (P < 0.05) increased from the basal level (0.49 +/- 0.05 vs. 0.29 +/- 0.03) (P < 0.01), while in platelets these changes were opposite (0.11 +/- 0.05 vs. 0.25 +/- 0.05) (P < 0.01). Compared to these significant changes, salt loading (200 mEq NaCl/day) for 6 days decreased PRA(0.49 +/- 0.10 vs. 1.05 +/- 0.17 ng/l/s; P < 0.01) and induced the opposite changes in the ratio of AT1 receptor/GAPDH mRNA. These data suggest that AT1 receptors in human blood cells may be of two different types--platelets and mononuclear leucocytes.

Adult↗
PubMed1995

Synthesis and the stereoselective enzymatic hydrolysis of flurbiprofen-basic amino acid ethyl esters.

Ethyl esters of flurbiprofen L-arginine (FP-Arg-OH), flurbiprofen L-lysine (FP-Lys-OH) and flurbiprofen p-guanidino-L-phenylalanine (FP-GPA-OH) were synthesized and then the release of flurbiprofen enantiomers from these derivatives in the presence of trypsin (Tp), carboxypeptidase B (CPB) and carboxypeptidase Y (CPY) were examined in order to evaluate their availability as prodrugs for flurbiprofen (FP). The ester bonds of the three racemic FP derivatives were hydrolyzed by Tp at about 3 to 20 times the rates of N-benzoyl-L-arginine ethyl ester (Bz-Arg-OEt), a specific substrate for Tp. (R)-FP was released faster than (S)-FP by either CPB or CPY from both FP-Arg-OH and FP-Lys-OH. On the other hand, FP-GPA-OH was not hydrolyzed at all by CPB and the hydrolysis rate of this compound by CPY was very slow. (S)-Flurbiprofen L-arginine ethyl ester ((S)-FP-Arg-OEt) was separated from (R)-FP-Arg-OEt by high-performance liquid chromatography. A comparison of the kinetic parameters for the tryptic hydrolysis of the two optically active FP-Arg-OEt diastereomers and those of Bz-Arg-OEt suggested that the orientation of the scissile bond in each diastereomer to the catalytic center of Tp is more favorable than that of Bz-Arg-OEt. However, no significant difference was found between the kinetic parameters for the two diastereomers, suggesting that the orientational difference between (S)-FP and (R)-FP in the diastereomers does not have any effect on the tryptic hydrolysis of the ester bond.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1995

Production of thrombopoietin (TPO) by rat hepatocytes and hepatoma cell lines.

Recently, we purified rat thrombopoietin (TPO) from plasma of irradiated rats (XRP) by measuring its activity that stimulated the production of megakaryocytes from megakaryocyte progenitor cells (CFU-MK) in vitro. We then cloned the cDNAs for rat and human TPO. In this study, we found the production of TPO by hepatocytes isolated with the collagenase perfusion method from both normal and thrombocytopenic rats, by a two-step fractionation of hepatocyte culture medium (CM). Subsequently, CM of rat hepatoma cell lines was screened for the presence of TPO; three cell lines, H4-II-E, McA-RH8994, and HTC, were found to produce TPO. According to the purification procedure for TPO from XRP, TPO was partially purified from 2 L CM of each of three cell lines with a six-step procedure. In the final reverse-phase column, TPO from each cell line was eluted with the same retention time as that from XRP, and the TPO fraction exhibited megakaryocyte colony-stimulating activity (Meg-CSA). TPO-active fraction eluted from the final reverse-phase column was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), extracted from the gel, and assayed. TPO activity from each cell line was found in the respective molecular weight region, indicating the heterogeneity of the TPO molecule. Using reverse transcriptase-polymerase chain reaction (RT-PCR), we detected the expression of TPO mRNA in hepatocytes, three hepatoma cell lines, normal rat liver, and X-irradiated rat liver. Northern blot analysis showed that TPO mRNA was expressed mainly in liver among the various organs tested. These data demonstrate that TPO is produced by rat hepatocytes and hepatoma cell lines and suggest that liver may be the primary organ that produces TPO.

Animals↗
PubMed1995

A simple and quantitative liquid culture system to measure megakaryocyte growth using highly purified CFU-MK.

A new and quantitative liquid culture system has been developed to measure the production of megakaryocytes from megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]). The system uses as a target population a glycoprotein (Gp) IIb/IIIa+ subpopulation of rat bone marrow cells previously demonstrated to be highly enriched for CFU-MK. GpIIb/IIIa+ cells were cultured at 5 x 10(4) cells/mL (10(4) cells/well) with test samples in 96-well tissue culture plates for 4 days at 37 degrees C. During the final 3 hours of incubation, the cells were pulsed with [14C]5-hydroxytryptamine creatinine sulfate (14C-serotonin). After incubation, the plates were washed and the cell pellets were lysed with Triton-X 100. The cell lysate was infiltrated into a commercially available solid scintillator and dried, and radioactivity was measured. In this assay system, rat interleukin-3 (IL-3) was found to be the most potent among known cytokines tested. Murine granulocyte-macrophage colony-stimulating factor (GM-CSF), human erythropoietin (Epo), human IL-6, and murine stem cell factor (SCF) each alone stimulated megakaryocyte growth but were much less active than rat IL-3. Plasma of rats rendered thrombocytopenic by injection of monoclonal antirat platelet GpIIb/IIIa antibody exhibited significant activity, and the active protein fractions partially purified from the plasma showed much higher activity, but normal rat plasma had no effect. This liquid culture system allows the measurement of a large number of test samples--including a wide variety of cytokines and unknown growth factors, alone or in combinations--and provides a simple method for evaluating the early proliferative events involving CFU-MK in the megakaryocyte differentiation pathway.

Animals↗
PubMed1995

Hamster alpha 1B-adrenergic receptor directly activates Gs in the transfected Chinese hamster ovary cells.

A prototypic Ca(2+)-mobilizing hormone receptor, alpha 1-adrenergic receptor (alpha 1AR), stimulates cAMP accumulation. The mechanism underlying this phenomenon was previously suggested to be secondary to phosphatidylinositol hydrolysis-protein kinase C activation in some cells. We transfected Chinese hamster ovary (CHO)-K1 cells with hamster alpha(1B)AR cDNA and isolated cells stably expressing alpha(1B)AR (CHO alpha 1B cells). We investigated the molecular mechanism underlying the alpha 1AR-mediated cAMP production in the CHO alpha 1B cells. Norepinephrine (NE) stimulated intracellular calcium mobilization and cAMP production through alpha(1B)AR. Pretreatment with a phospholipase C inhibitor, U-73,122 (10 microM), abolished the NE-induced intracellular calcium response, whereas it did not affect the NE-stimulated cAMP production. Treatment with various agents (protein kinase C inhibitors, calcium ionophore, cyclo-oxygenase inhibitor, or pertussis toxin) had little effect on the NE-induced cAMP production. The parent CHO and CHO alpha 1B cells contained similar amounts of Gs alpha (42 and 45 kDa, respectively), as detected with immunoblot analysis, and exhibited similar extents of cAMP synthesis with cholera toxin and forskolin. Adenylyl cyclase activity in the CHO alpha 1B cell membranes was also enhanced by NE. Furthermore, incubation of CHO alpha 1B cell membranes with antiserum directed against the carboxyl-terminal portion of Gs alpha inhibited the NE-stimulated adenylyl cyclase activity. Taken together, the results indicate that the alpha(1B)AR-mediated cAMP synthesis in CHO alpha 1B cells reflects direct stimulation of Gs-adenylyl cyclase. Therefore, the alpha 1AR-stimulated cAMP production observed in some native tissues may involve the multiple mechanisms of the direct activation of Gs-adenylyl cyclase and a secondary effect through activation of phosphatidylinositol hydrolysis.

Adenylate Cyclase Toxin↗
PubMed1995

KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues.

alpha 1-Adrenoceptors (ARs) comprise a heterogeneous family, and subtype-selective ligands are valuable for studying the functional role of each receptor subtype. We characterized a newly synthesized, alpha 1-AR antagonist, KMD-3213, by using Chinese hamster ovary cells stably expressing the three cloned human alpha 1-ARs (alpha 1a, alpha 1b, and alpha 1d), as well as native rat and human tissues. KMD-3213 potently inhibited 2-[2-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but had 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively. KMD-3213 inhibited norepinephrine-induced increases in intracellular Ca2+ concentrations in alpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effect on the alpha 1b- and alpha 1d-ARs. Using pharmacologically well characterized native rat tissues [submaxillary gland (alpha 1A-AR-expressing tissue), liver (alpha 1B-AR-expressing tissue), and heart (mixed alpha 1A- and alpha 1B-AR-expressing tissue)], binding studies showed that inhibition curves for KMD-3213 in submaxillary gland and liver best fit a one-site model (with Ki values of 0.15 and 16 nM, respectively), whereas KMD-3213 had high and low affinity sites in heart membranes. Chloroethylclonidine treatment of rat heart membranes completely eliminated the low affinity sites for KMD-3213. Furthermore, in human liver and prostate KMD-3213 could identify high and low affinity sites, the Ki values of which corresponded well to those for the cloned human alpha 1a- and alpha 1b-ARs, respectively. Moreover, the affinity of KMD-3213 was found to be approximately 10-fold higher at the cloned human alpha 1a-AR than at the cloned rat alpha 1a-AR. KMD-3213 is a potent and highly selective antagonist for the human alpha 1a-AR and would be useful for studying the physiological roles of human alpha 1-AR subtypes.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

D-Val22 containing human big endothelin-1 analog, [D-Val22]Big ET-1[16-38], inhibits the endothelin converting enzyme.

Endothelin converting enzyme (ECE) is essential for generation of the biological effects of endothelin-1 (ET-1) from a precursor, big endothelin-1 (Big ET-1). We synthesized four analogs of human Big ET-1[16-38], substituted with single D-amino acids at P1, P2, P1' and P2' positions. ECE activity was determined using an ET-1 specific radioimmunoassay system. None of the D-amino acid containing Big ET-1 analogs were apparently cleaved by ECE, however, one of the synthetic peptides, [D-Val22]Big ET-1[16-38], strongly inhibited the ECE activity. Furthermore, when this D-Val22 containing peptide was preadministered to rat striatum, it was found to inhibit the dopamine release induced by Big ET-1. This result suggests that the D-Val22 containing peptide inhibits the ECE activity in vivo. The D-Val22 containing inhibitor offers hope of developing more potent and highly specific ECE inhibitors of therapeutic significance.

Amino Acid Sequence↗