Biomedical subjects

J W Ryan

Publications and source records attributed to J W Ryan.

At least 37 records · Page 2Linked to original sources

PubMed1994

Immunoaffinity purifications of aminopeptidase P from guinea pig lungs, kidney and serum.

Previously, aminopeptidase P (AmP) has been purified from mammalian tissues by highly laborious multistep chromatography procedures. To simplify purifications, we raised a monoclonal antibody to guinea pig serum AmP and used the antibody to prepare an immunoaffinity matrix. The immunoaffinity matrix was used to obtain highly purified forms of AmP from guinea pig lungs, kidney and serum. The antibody is reactive with rat and human forms of AmP and may simplify procedures needed for their purifications.

Amino Acid Sequence↗

PubMed1994

Assay of pulmonary microvascular endothelial angiotensin-converting enzyme in vivo: comparison of three probes.

We monitored the activity of pulmonary microvascular endothelial-bound angiotensin-converting enzyme (ACE) in vivo by means of multiple indicator-dilution-type techniques, utilizing three different probes: the hydrolysis of two substrates, [3H]-benzoyl-Phe-Ala-Pro (BPAP) and [14C]benzoyl-Ala-Gly-Pro (BAGP), and the binding of the inhibitor [3H]RAC-X-65 (RAC), all measured during a single transpulmonary passage in anesthetized rabbits, placed on total heart bypass, so that both systemic and pulmonary circulations were fully supported by means of a two-channel extracorporeal pump. Experiments were performed at pulmonary blood flows (Qb) of 250, 400, 560, and 800 ml/min in control or indomethacin-pretreated rabbits. ACE activity was also compared to that of pulmonary microvascular endothelial-bound 5'-nucleotidase, by measuring the dephosphorylation of its natural substrate 5'-[14C]AMP. We calculated substrate utilization, mean lung transit time (t), and volume of distribution (i.e., central blood volume) of all substrates, as well as inhibitor binding. We also calculated Amax/Km and Bmax products of enzyme mass and kinetic constants for substrates and inhibitor, respectively. As Qb increased, Amax/Km values for all three substrates and Bmax increased linearly, indicating microvascular recruitment. In experiments in which either BPAP and 5'-AMP metabolism or BAGP metabolism and RAC binding were studied concomitantly, a linear relationship was observed between Qb-induced changes in Amax/Km values of BPAP vs 5'-AMP as well as in Amax/Km of BAGP vs Bmax of RAC. Similarly, increasing Qb increased central blood volume and decreased t. Indomethacin had no effect on most of the hemodynamic or enzyme parameters measured. We conclude that in vivo assays of ACE proceed as predicted by Michaelis-Menten kinetics and offer insights into pulmonary endothelial pathophysiology.

Animals↗

PubMed1994

Radiation-induced early pulmonary endothelial ectoenzyme dysfunction in vivo: effect of indomethacin.

We investigated the early effects of radiation on pulmonary endothelial function in vivo 7-8 hr after exposure of rabbits to a single dose of 30 Gy to the chest. Utilizing multiple indicator-dilution techniques, we measured rates and kinetics of hydrolysis of the synthetic substrates [3H]benzoyl-Phe-Ala-Pro (BPAP) and [14C]benzoyl-Ala-Gly-Pro (BAGP) by endothelial-bound angiotensin-converting enzyme (ACE) and of 5'[14C]-AMP by endothelial-bound 5'-nucleotidase (NCT) and binding of the synthetic ACE inhibitor [3H]RAC-X-65 during a single transpulmonary passage in anesthetized, artificially ventilated, open-chest rabbits in which both systemic and pulmonary circulations were fully supported by an extracorporeal pump. We have shown that these techniques and the use of the aforementioned probes provide reliable information on pulmonary endothelial function in vivo. Radiation to the chest produced endothelial ectoenzyme dysfunction, as reflected in altered available perfused capillary surface area and altered enzyme kinetics of all probes (decreases in substrate hydrolysis, inhibitor binding, first- and second-order kinetic constants) over a wide range of pulmonary blood flow values (reflecting approximately 60-200% of normal cardiac output). Indomethacin prevented most of these alterations in partially as well as fully recruited lungs. We conclude that impairment of endothelial ectoenzyme activity is an early event in the pathogenesis of radiation-induced lung damage, which occurs independently of hemodynamic influences and may involve synthesis of arachidonic acid metabolites.

Animals↗

PubMed1994

Characterization of rat pulmonary vascular aminopeptidase P in vivo: role in the inactivation of bradykinin.

The nonapeptide bradykinin (BK) is hydrolyzed at multiple sites during a single passage through the rat pulmonary vascular bed. Hydrolysis of one bond, Arg1-Pro2, appears to be catalyzed by an aminoacylproline hydrolase called aminopeptidase P (AmP). To help clarify its role in BK degradation, we have characterized rat pulmonary AmP in vivo in terms of its ability to react with intravascular substrates, its saturability and its contributions to the inactivation of circulating BK. By using indicator dilution methodology, hydrolysis of tracer doses of the AmP substrate Arg-Pro-Pro-[3H]benzylamide ([3H]APPB) during a single transit through the pulmonary vascular bed was measured. Transpulmonary hydrolysis of [3H]APPB obeyed first-order enzyme kinetics and was inhibited by carrier substrate (APPB) and two alternative AmP substrates, BK and des-Arg9-BK. APPB, des-Arg9-BK and des-Arg1-BK, all capable of binding to AmP in vitro, potentiated hypotensive effects of BK injected i.v. A saturating dose of APPB, 2 mumol/kg, in coinjections with BK, potentiated effects of i.v. BK by about 4-fold when pulmonary angiotensin converting enzyme (ACE) was active or inhibited completely. Complete inhibition of ACE potentiated blood pressure effects of i.v. BK by 40- to 120-fold. When both AmP and ACE were inhibited, the effects of i.v. BK were potentiated by up to 800-fold, and the hypotensive effects of BK injected i.v. on systemic mean arterial blood pressure were equivalent to effects of BK injected into the ascending aorta (i.a.); the BK i.v. and i.a. log dose-response curves were virtually superimposable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopeptidases↗

PubMed1994

Estimation of rate constants for reactions of pulmonary microvascular angiotensin converting enzyme with an inhibitor and a substrate in vivo.

We developed a method of measuring the mole quantity of pulmonary angiotensin-converting enzyme (ACE) bound by a partially saturating dose of an ACE inhibitor injected i.v. For each test animal (11 guinea pigs), tracer (nonsaturating) doses of the ACE substrate [14C]benzoyl-Ala-Gly-Pro (14C-BAGP) and the ACE inhibitor 3H-RAC-X-65 were coinjected at timed intervals for a total of four studies per animal. The injectate used for the second study contained, in addition, a partially saturating dose of unlabeled RAC-X-65. With indicator-dilution techniques supplemented with measurements of fractional hydrolysis of 14CBAGP and uptake of 3H-RAC-X-65 during a single transit through the pulmonary vascular bed, the following parameters were computed: plasma flow (Qp), (kcat/Km)[E] vector c, k1[E] vector c and Eb, where [E] is the concentration of active ACE, Eb is the mole quantity of ACE bound by inhibitor, kcat/Km is the second-order rate constant for substrate hydrolysis, k1 is the inhibitor-ACE association rate constant and vector c is capillary mean transit time. As shown elsewhere (Catravas et al., 1990; Catravas and White, 1984), the product of Qp (in liters per second) multiplied by (kcat/Km)[E] vector c is (kcat/Km)E, and the product of Qp multiplied by k1[E] vector c is k1E, where E is the mole quantity of ACE. Values of (kcat/Km)Eb and k1Eb were computed and divided by Eb to obtain kcat/Km and k1. The fractional degree of inhibition conferred by a partially saturating dose of an ACE inhibitor can be understood to be the ratio Eb/ET, where ET is total ACE. With Eb in moles and the ratio Eb/ET, we computed the mole quantity of ET. By measuring the rate of recovery of ACE activity following partial inhibition of ACE, an apparent dissociation rate constant, k(dissoc), was computed. With k(dissoc) and K1, an apparent Ki was computed. The following computations were obtaine: ET of 0.90 +/- 0.20 (S.E.M.) nmol; kcat/Km, 5.16 +/- 0.89E + 06 M-1.sec-1; k1, 1.26 +/- 0.21E + 06 M-1.sec-1; k(dissoc), 6.47 +/- 0.63E - 04 sec-1 and Ki, 5.13E - 10 M. Although we focused on the characterization of ACE, the methods developed are general and may be applicable to studies of other vascular surface proteins, including other enzymes and hormone receptors.

Amino Acid Sequence↗

PubMed1993

N-glycosylation of forms of angiotensin converting enzyme from four mammalian species.

To help clarify bases for the molecular weight and surface charge heterogeneities of forms of somatic angiotensin converting enzyme (ACE), we examined for differences in N-glycosylation. ACE preparations purified from human, guinea pig, rat and rabbit tissues were found to be heterogeneous in terms of numbers of N-glycosylated sites (7-8 sites per molecule of ACE) and in types of structures of oligosaccharides used for glycosylation (complex versus high mannose oligosaccharide contents). Our findings, taken with reports of potential N-glycosylation sites and amino acid sequencing data, indicate that ACE forms can differ in terms of degrees of glycosylation, sites of glycosylation and structures of attached oligosaccharide units.

Animals↗

PubMed1993

A comparison of guinea pig serum angiotensin converting enzyme with forms of angiotensin converting enzyme from human, rat and rabbit tissues.

Guinea pig serum angiotensin converting enzyme (ACE) activities exceed ACE activities of other mammalian sera by as much as two magnitudes. To examine the possibility that guinea pig ACE has a superior catalytic efficiency, we purified it to apparent homogeneity and compared it to highly purified forms of ACE from human seminal plasma, rat lungs and rabbit lungs. The first 24 amino acid residues of guinea pig and rat ACE forms were 96% identical with the sequence of human ACE. Second order rate constants (kcat/Km) for guinea pig, human and rabbit forms of ACE on reaction with benzoyl-Phe-Ala-Pro were identical (1.6E-09 M-1 min-1). Their dissociation constants on reaction with the ACE inhibitor RAC-X-65 were within a narrow range (10-16 pM). Thus, the high ACE activity of guinea pig serum is owing to high enzyme concentration and not to superior catalytic efficiency.

Amino Acid Sequence↗

PubMed1993

Immunoscintigraphy in primary colorectal cancer.

Immunoscintigraphy is an experimental diagnostic nuclear medicine imaging technique that targets tumor sites with radiolabeled antibodies reactive with tumor-associated antigens. Primary tumors, regional lymph node metastases, and distant metastases have been imaged in patients with colorectal cancer, and United States Food and Drug Administration (FDA) approval of a commercial preparation of radiolabeled murine monoclonal antibodies for diagnostic use in such patients is expected soon. Immunoscintigraphy is complementary to computed tomography (CT) scanning in the evaluation of the abdomen and pelvis in patients with colorectal cancer, and it has the additional capability of serial whole body imaging for detection of distant metastases. However, the clinical utility of immunoscintigraphy is being investigated, and its precise diagnostic role in patients with primary colorectal cancer has not been adequately defined. The management of selected patients at increased risk of regional or distant spread of tumor likely would benefit from detection of occult disease and a change in clinical staging, but the routine use of immunoscintigraphy in the preoperative evaluation of patients with primary colorectal cancer is more problematic. More studies are required to determine whether it should be used to stage all patients before operation or merely be reserved for selected patients at increased risk for metastatic disease.

Colonic Neoplasms↗

PubMed1993

A radiochemical assay for aminopeptidase N.

We developed an assay for aminopeptidase N (AmN) in which substrate, Arg-Phe-[3H]anilide (24.9 Ci/mmol), can be used at concentrations (1-200 nM) well below Km (12 microM) and at or below enzyme concentration ([E]). Such reaction conditions simulate those in vivo where peptide hormones in picomolar concentrations (<< Km) are degraded by nano- or micromolar concentrations of enzyme. The Arg-Phe-[3H]anilide:AmN reaction obeyed first-order enzyme kinetics when human serum, human seminal plasma, guinea pig serum, or homogeneous porcine kidney AmN was used as enzyme source and substrate was within the concentration range of 1-200 nM. For porcine AmN, kcat/Km was 1.47 x 10(9) M-1 min-1, kcat 17,640 min-1. Human serum AmN was in a concentration (about 4.6 nM) in great excess over those reported for substrates such as angiotensin III. Several advantages accrue under conditions of first-order enzyme kinetics: (1) Vmax/Km is measured directly. (2) When kcat/Km is known, [E] can be computed in mol/liter. (3) IC50 values for alternative substrates can be taken as Km values. (4) IC50 values for inhibitors are Ki values when Ki >> [E]. Arg-Phe-[3H]anilide can be used to measure AmN activity in the presence of chromophores and fluorophores that interfere with photometric and fluorometric assays. We have confirmed that alleged substrates such as angiotensin III and Met-Lys- and Lys-bradykinin are bound by AmN with high affinities (Km values, 5.7, 9.1, and 14.3 microM). Bovine pulmonary artery endothelial cell cultures were found to possess AmN-like activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Angiotensin-converting enzyme inhibitors have no effect on ovulation and ovarian steroidogenesis in the perfused rat ovary.

The null hypothesis of this study was that the angiotensin-converting enzyme inhibitors, captopril and teprotide, would not reduce the number of ovulations in vivo and in vitro in the rat. Captopril (in three regimens) was administered continuously beginning prior to pregnant mare's serum gonadotropin and hCG to trigger ovulation. The number of in vivo ovulations were counted. Ovaries similarly primed with pregnant mare's serum gonadotropin were dissected and perfused in media with hCG and captopril (two regimens) or teprotide (one regimen). The number of in vitro ovulations and steroid production in the perfusions were evaluated. The results were evaluated by the Student's t test. Power calculations gave only a 20% chance of missing a 16% difference in ovulations or steroidogenesis. There was no inhibition of ovulation or change in steroid production in angiotensin-converting enzyme treated rats in vivo or in vitro. While angiotensin II has been shown to be an important mediator in the mechanism of ovulation, angiotensin-converting enzyme inhibition via captopril or teprotide does not result in angiotensin II antagonistic effects. Hypothetical mechanisms to explain this paradox are presented.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Near falls incidence. A study of older adults in the community.

1. Although falls in older adults have been studied in a variety of settings, near falls (or almost falling) have received little or no attention--and therefore their clinical relevance is unknown. 2. Older adults were able to discriminate between near fall and actual fall events without difficulty. 3. Thirty-five percent of the older adults who participated in this study experienced near falls in the 3-weeks of data collection. Therefore, near falls are common events in the lives of many older adults.

Accidental Falls↗

PubMed1992

A radioassay for aminoacylproline hydrolase (aminopeptidase P) activity.

A radioassay was developed in which aminoacylproline hydrolase acts on Arg-Pro-Pro-[3H]benzylamide to yield arginine plus Pro-Pro-[3H]benzylamide. By stopping the reaction with base (0.1 M NaOH), the radioactive product is deprotonated to an organophilic form and is separable from the hydrophilic substrate by extraction of the alkaline aqueous solution with an organic solvent. When scintillants are included in the organic solvent, the enzyme:substrate reaction, extraction and quantification of Pro-Pro-[3H]benzylamide can all be conducted using a single liquid scintillation vial. Thus, aminoacylproline hydrolase activity is measured in terms of the rate of release of Pro-Pro-[3H]benzylamide. The substrate is obtainable at greater than 20 Ci/mmol, which enables its use under conditions of first-order enzyme kinetics. Conditions of near-zero order kinetics are readily attained by adding unlabeled substrate (Km 0.7 microM). The substrate is highly reactive (a 1:2000 dilution of guinea pig plasma hydrolyzed greater than 10% of the substrate during a 10 min incubation at 37 degrees C) and specific in that it is not degraded by leucine aminopeptidase, aminopeptidase A or N, dipeptidyl peptidase IV nor prolyl endopeptidase. The assay was used to measure aminoacylproline hydrolase specific activities in tissues of rat and guinea pig. Activity was found in virtually all major tissues of both species, and some guinea pig tissues (e.g. kidney and plasma) were found to be notably rich sources of the enzyme.

Amino Acid Sequence↗

PubMed1992

Purification and characterization of guinea pig serum aminoacylproline hydrolase (aminopeptidase P).

Aminoacylproline hydrolase (EC 3.4.11.9) of guinea pig serum has been obtained as two apparently homogeneous isoforms. Dialyzed serum was chromatographed successively on Affi-gel blue, hydroxyapatite, DE-cellulose, phenyl-Sepharose, an affinity matrix for angiotensin converting enzyme and concanavalin-Sepharose. On the latter matrix, 68% of the enzyme activity was eluted with alpha-methyl mannoside at 10 and 100 mM, and 29% was eluted with alpha-methyl glucoside, 500 mM, at 56 degrees C. The two fractions ('biantennary' and 'high mannose' fractions, respectively) were concentrated and then chromatographed separately on Sephacryl S-200HR. Both fractions were eluted as expected for a globular protein of Mr 217,000. On SDS-PAGE, under reducing and non-reducing conditions, each of the concanavalin-Sepharose fractions was separated into two protein bands, Mr 89,000 and Mr 81,500. Each of the bands was found to be N-blocked when N-terminal amino acid sequencing was attempted. The reaction of the 'biantennary' fraction with the synthetic substrate Arg-Pro-Pro-[3H]benzylamide was characterized in part: Km 0.7 microM, kcat 124.6 min-1, kcat/Km 1.78.10(8) M-1 min-1. Hydrolysis of the substrate was strongly inhibited by bradykinin and those of its lower homologs that contain two adjacent proline residues. Cu2+ was strongly inhibitory. Co2+ at 30 microM activated the enzyme, as did Mn2+, Mg2+ and Ca2+ at higher concentrations. Sulfhydryl compounds, including captopril, inhibited the enzyme as did 1,10-phenanthroline. Iodoacetamide and N-ethylmaleimide had no effects, but 4-hydroxymercuribenzoate conferred a partial inhibition over a remarkably wide concentration range: 0.34-1400 microM. Amastatin and bestatin did not inhibit the enzyme. Aminoacylproline hydrolase of guinea pig serum appears to be a heterogeneous, glycosylated metallo-enzyme with a high affinity for bradykinin and related peptides in which the sequence Pro-Pro, Xaa-Pro-Pro or Xaa-Pro-Hyp is N-terminal.

Amino Acid Sequence↗

PubMed1992

Pulmonary angiotensin-converting enzyme substrate hydrolysis during exercise.

We examined exercise-induced changes in indicator-dilution estimates of the angiotensin-converting enzyme first-order kinetic parameter, the ratio of a normalized maximal enzymatic conversion rate to the Michaelis constant (Amax/Km), which, under stable enzymatic conditions, will vary with the pulmonary vascular surface area accessible to vascular substrate, the extravascular lung water (an index of the proportion of lung tissue perfused), and the central blood volume (from pulmonary trunk to aorta). Experiments were performed in 10 mongrel dogs at rest and through two increasing levels of treadmill exercise, with the use of two vascular space tracers (labeled erythrocytes and albumin), a water space tracer ([1,8-14C]-octanediol), and a vascular endothelium surface area marker, benzoyl-Phe-Gly-Pro ([3H]BPGP), which is a pharmacologically inactive angiotensin-converting enzyme substrate. The exercise-induced increase in cardiac output was accompanied by a linear increase in central blood volume, and dilutional extravascular lung water rapidly increased to an asymptotic proportion close to 100% of postmortem vascular lung water. There was an average 55% [3H]BPGP hydrolysis, which did not vary with flow, and the computed Amax/Km increased linearly with exercise. We conclude that exercise results in complete lung tissue recruitment and increases the pulmonary vascular surface area available for BPGP hydrolysis linearly with flow, so that pulmonary vascular recruitment continues after full tissue recruitment.

Amino Acid Sequence↗

PubMed1992

Influence of vascular smooth muscle heterogeneity on angiotensin converting enzyme activity in chicken embryonic aorta and in endothelial cells in culture.

The smooth muscle of the abdominal region of the chicken aorta derives from locally recruited mesenchyme (mesenchymal smooth muscle), whereas that of the thoracic region derives from the neural crest (ectomesenchymal smooth muscle). We hypothesized that this smooth muscle heterogeneity might affect important enzymatic functions of the vessel wall. Therefore, we measured angiotensin converting enzyme (ACE) activity in homogenates of chicken thoracic and abdominal aorta at different embryonic stages (days 10, 14, and 18 of gestation). ACE activity increased in both regions over the time of gestation (p less than 0.001 in both cases); the increase was steeper and ACE activity was higher in thoracic than in abdominal segments (p less than 0.001). Km values were similar (approximately 7 microM) at all times and between the two segments, whereas changes in Vmax values closely paralleled those in enzyme activity, indicating gestation-dependent increases in the amount of enzyme. Neural crest ablation at an early developmental stage resulted in an increase of ACE activity in thoracic homogenates (p less than 0.001), predictably leaving that in abdominal homogenates unaffected. Bovine pulmonary artery endothelial cell monolayers exposed to media conditioned with cultured mesenchymal or ectomesenchymal smooth muscle cells exhibited elevated ACE activity (46% and 83%, respectively, relative to control medium, with p less than 0.01 in both cases; p less than 0.05 between the two media). Increases in endothelial cell ACE activity corresponded to proportional increases in ACE protein determined by enzyme-linked immunosorbent assay (r = 0.99) and were interpreted as indicative of enhanced enzyme synthesis subsequent to exposure of endothelial cells to smooth muscle-conditioned media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The Patient Intensity for Nursing Index: a validity assessment.

The psychometric assessment of a new measure of nursing intensity, The Patient Intensity for Nursing Index (PINI) is reported. Four dimensions of nursing intensity are measured by the PINI: (a) severity of illness, (b) dependency, (c) complexity of care, and (d) time. There are 10 items rated on a 5-point ordinal scale. A purposively drawn sample of 6,445 patients was obtained from five hospitals, with 487 registered nurses (RNs) providing daily patient ratings from 29 medical-surgical and intensive care units. Substantial interrater reliability was demonstrated. Validity testing included confirmatory factor analysis, hypothesis-testing, contrasted groups, and an observational study of time. The factor structure confirmed specified components of severity, dependency, and complexity, with time loading on all three factors. PINI scores were significantly related to medical severity of illness, length of hospital stay, disposition at discharge, number of secondary medical diagnoses and specialty consults, and scores on three different hospital classification systems used for staffing. PINI scores were significantly different for high- and low-intensity DRGs. Observed time spent delivering nursing care to specific patients was significantly correlated with nurse estimates of time.

Dependency, Psychological↗

PubMed1991

Changing how nurses spend their time.

The results of work sampling studies are used to examine how nurses spend their time and to relate nurses' time to the shortage of nursing practice in hospitals. Four types of proposals for improving the delivery of nursing care in hospitals are discussed. The likely impact of these proposals on how nurses spend their time and the consequences of increasing the effectiveness of professional nursing practice are explored.

Career Mobility↗

PubMed1991

Species variation in pulmonary endothelial aminopeptidase P activity.

Pulmonary endothelial aminopeptidase P (AmP) may be an important contributor to the inactivation of circulating bradykinin in certain species. To examine this possibility, we measured AMP activity in vivo and in vitro using Arg-Pro-Pro-[3H]benzylamide (3H-APPB) as substrate under conditions of first order enzyme kinetics. Utilizing multiple indicator dilution techniques, metabolism of 3H-APPB to Arg and Pro-Pro-[3H]benzylamide by AmP was not detectable during a single transpulmonary passage in anesthetized rabbits (n = 4), cats (n = 3) and pigs (n = 4). However, percent metabolism of 3H-APPB ranged from 54 to 63% in anesthetized rats (n = 6). In all experiments, the substrate remained within the vascular space and was thus accessible to endothelial and blood AmP only. At the same time, single-pass transpulmonary percent metabolism of [14C]benzoyl-Ala-Gly-Pro by endothelial-bound angiotensin converting enzyme was remarkably similar among rabbits, cats, rats and pigs (60-65%). In culture, Vmax/Km of AmP was 3 to 10 x 10(-4) min-1 for human basal arterial and rabbit and bovine pulmonary arterial endothelial cell monolayers (2 x 10(5) cells). AmP activity in the supernatant of lung and kidney tissue (homogenized in saline containing 1-o-n-octyl-beta-glucopyranoside) from rabbit, cat, pig and rat expressed as Vmax/Km(min-1) per (g wet tissue/ml) was 0.74, 2.25, 3.91 and 185.8 (lung), and 1.0, 3.7, 8.4 and 438.3 (kidney), respectively. Similarly, Vmax/Km values of AmP in plasmas of cat, dog, rabbit, pig, calf (serum), human and rat were 0, 0.016, 0.025, 0.068, 0.191, 0.237 and 3.53 min-1. These results suggest that 1) there are large interspecies variations in AmP activities of plasma, lung and kidney; 2) of the species studied, the rat contains the largest activities of AmP; and 3) AmP appears to be located on the luminal surface of the rat pulmonary endothelium.

Aminopeptidases↗