Gastric and cardiovascular effects of histamine in the dog

The H-2 receptor stimulation of gastric acid secretion and of heart rate by histamine, a mixed H-1–H-2 agonist, given in 45-min successive step doses 2–150 g base/kg.h and 4(Me)histamine, (4(Me)H), 1.4 to 210 g base/kg.h, a specific H-2 agonist, in five conscious gastric fistula dogs showed no difference between the agonists in ED₅₀s or in maximal responses. The ED₅₀ for acid was lower (15–16 g/kg.h) than for cardiac chronotropism (25 to 27 g/kg.h). Both effects were competitively antagonized by the H-2 antagonist cimetidine, 0.5 to 1 mg/kg.h. Background infusions of diphenhydramine, 2 mg/kg.h, raised the maximum heart rate increase caused by histamine from +108 to +149 beats/min (p<0.05) but not that of 4(Me)H; acid outputs were not augmented. Diphenhydramine 2 mg/kg.h alone caused no significant change in heart rate or blood pressure. Histamine reduced systolic blood pressure (SBP) by 48 mmHg and with diphenhydramine background by 61 mmHg (p<0.05). 4(Me)H at a top dose of 210 g base/kg.h reduced SBP by 81 mmHg (p<0.05). To test whether the effects of added diphenhydramine could be interpreted as an H-1 receptor effect of histamine, the H-1 agonist 2-pyridylethylamine (PEA) was given alone (2–150 g/kg.h in 45-min steps) or as a 100 g/kg bolus during the infusion of 4(Me)H 50 g/kg.h. There was no effect of PEA on gastric acid, heart rate or blood pressure. Even though diphenhydramine augments the effect of histamine on heart rate and blood pressure, the lack of PEA effect would indicate that there is not a direct H-1 receptor mediated effect on gastric acid, heart rate or systolic blood pressure in the conscious dog. This contrasts with published data obtained in anesthetized animals. After a single dose of 4(Me)H, 50 g/kg.h had been infused i.v. for 45 min, acid output had reached 70% of the maximum seen at 90 min, heart rate had increased by 65% of its maximum response but SBP had not yet changed. Cimetidine blocked 4(Me)H-induced hypotension completely but blocked the heart rate increase only partially and competitively. We conclude that in the intact animal there is evidence for a direct H-2 mediated stimulation of heart rate in the conscious dog with kinetics similar to the H-2 stimulation of gastric acid secretion.Supported by Research Grant No. AM09260 from the National Institute of Arthritis, Metabolism and Digestive Diseases, National Institutes of Health and by the Medical Research Service of the Veterans Administration.     

Renal function in relation to three candidate genes in a Chinese population

We recently found in a white population that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), -adducin (Gly460Trp), and aldosterone synthase (–344C/T) jointly influence renal function. We therefore investigated in a Chinese population the associations between the serum concentrations of creatinine and uric acid and these three genetic polymorphisms. We genotyped 471 ethnic Han Chinese subjects from 125 nuclear families recruited in northern China via random population sampling (75%) and at specialized hypertension clinics (25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. The participants were 39.7 years old and included 235 women (49.9%). The blood pressure measured at the subjects homes averaged 126/80 mmHg. Mean values were 71 µmol/l for serum creatinine, 111 ml min^–1 1.73 m^–2 for calculated creatinine clearance, and 236 µmol/l for serum uric acid. With adjustment for covariables, GEE analyses of single genes demonstrated that serum uric acid, but not serum creatinine, was positively associated with the ACE D allele. Serum uric acid concentrations were 15.8 µmol/l (95% confidence interval 3.3–28.2) and 25.7 µmol/l (11.1–40.2) higher in DD homozygotes than in ID and II subjects, respectively. Further GEE analyses of the three genes combined showed that the association between serum uric acid and the ACE polymorphism was confined to carriers of the -adducin Gly and/or aldosterone synthase C alleles. Sensitivity analyses in parents and offspring separately as well as QTDT analyses were confirmatory. Among 114 informative offspring carrying the -adducin Gly allele serum uric acid was significantly and positively associated with the transmission of the ACE D allele (=20.7 µmol/l). In conclusion, the present study extends our previous findings on the combined effects of the three candidate genes and supports the concept that these genetic polymorphisms jointly influence renal function.     

Handling of allantoin by the rat kidney

Summary Renal excretion of allantoin was measured by tracer techniques. After injection of 2-C14 urate and H3 inulin, clearances of allantoin and inulin were measured and both proximal and distal tubules were micropunctured.In confirmation of earlier results 2-C14 urate injected into an intact animal is very rapidly converted to C14 allantoin: after 15 min more than 90% of urinary tracer is present as allantoin. It was further observed that 1) allantoin clearance is essentially identical with inulin clearance over a wide range of urine flows; 2) no net transport of allantoin occurs in either proximal or distal tubules. Clearly allantoin is handled by the rat kidney like inulin.The total excretion of filtered allantoin unlike that of filtered urate provides an easy and effective mechanism for animals possessing the enzyme uricase to dispose of their purine loads.Partially supported by the Österreichischer Fonds zur Förderung der wissenschaftlichen Forschung.Receiving scholarships from Deutsche Forschungsgemeinschaft.     

Intrinsic cholinergic excitation in the rat neostriatum: Nicotinic and muscarinic receptors

Summary An in vitro slice technique was employed to study the receptors involved in intrinsic cholinergic excitation in the rat neostriatum. The locally evoked synaptic potentials were suppressed by antinicotinic agents, mecamylamine (10 M), d-tubocurarine (3 M) or hexamethonium (100 M), but not by the antimuscarinic agent atropine (100 M). If the slices were exposed to an acetylcholinesterase (AChE)-inhibitor (paraoxon 1–20 M, physostigmine 0.1–0.5 M), the synaptic potentials were potentiated. The amplitude of the orthodromic population spike increased, and it was further facilitated when the stimulus frequencies were raised from 1–3 Hz to 10–30 Hz. The frequency facilitation following exposure to an AChE-inhibitor was blocked by atropine (1–100 M). Intracellular recording indicated that a slow depolarizing potential caused the frequency potentiation of the orthodromic discharges. Apparently rat neostriatum is similar to cholinergic systems in sympathetic ganglia and spinal Renshaw cells, in that nicotinic receptors mediate fast excitation and muscarinic receptors mediate slow excitation.     

Changes in blood cholesterol,protein fractions,and lipoproteins in functional disturbances of the central nervous system

Summary In experiments on 8 rabbits a study was made of the effect produced by nervous disorders on the protein-lipid composition of the blood. The method of electrophoresis of proteins and lipoproteins was used. In neurosis there is a drop of the total blood chlesterol, in the majority of the cases following a brief rise of its concentration in the blood; the percentage content of albumins fall with a corresponding rise of the -and, in individual cases, of the -and -globulin fractions. The -/-lipoproteins ratio increases. Observations carried out testify to an important role played by the CNS in the control of cholesterol, lipid, and protein metabolism.Presented by Active Member AMN SSSR, A. V. Lebedinskii Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 1, pp. 30–32, January, 1964     

Isolation and characterization of Chinese hamster ovary cell mutants resistant to the amino acid analogβ-aspartyl hydroxamate

Chinese hamster ovary cell lines which are resistant to an amino acid analog, -aspartyl hydroxamate, have been isolated and characterized. Mutants resistant to 100–150 M -aspartyl hydroxamate arose from ethyl methane sulfonate-treated parental lines at frequencies of 3.4×10^–6 to 1.3 ×10^–7. The mutants fell into at least two genetic classes: 18% of the mutants behaved codominantly in hybrids, the others recessively. Complementation studies indicated that all the recessive mutants belonged to the same class. Mutants selected after one step of mutagenesis overproduce the enzyme asparagine synthetase constitutively with four- to sixfold increases in specific activities over the basal levels of the parental lines. -Aspartyl hydroxamate-resistant cell lines with up to 20-fold elevations in asparagine synthetase activity have been isolated after two steps of mutagenesis. In addition, highly resistant lines have been selected by long-term growth of a dominant mutant in increasing concentrations of the drug. Resistance in the latter appears to be due not only to overproduction of asparagine synthetase but also to an alteration in the affinity of the enzyme for -aspartyl hydroxamate.     

Free fatty acidemia as an inducer of systemic hyperfibrinogenemia and fibrinolytic inhibition

Many major inflammatory stimuli induce secondary conditions of blood hyperfibrinogenemia and fibrinolytic inhibition, changes which may be mediated by alterations in free fatty acid (FFA) metabolism. The effect of a free fatty acidemia induced by the intravenous infusion of a triglyceride into rabbits on the fibrinogen/fibrinolytic system was determined. A 3-h infusion of synthetic fat emulsion induced a rapid rise in FFA (0.4–2.1Eq/ml in 3 h) followed by a more gradual rise in fibrinogen (2.6–4.3 mg/ml at 24 h), ₁-antitrypsin (1.1–1.9 mg/ml at 48 h), and serum fibrinolysis inhibitory activity (increased 202% at 48 h). Increases in protein concentration were due to increased synthesis. It is proposed that the changes in the fibrinogen/fibrinolytic system which follow major inflammatory stimuli are induced by a mediating free fatty acidemia. Possible pharmacological procedures to block these changes are discussed.     

Scanning electron microscopy of merogonous stages ofEimeria falciformis var.pragensis inMus musculus

Asexual stages ofEimeria falciformis var.pragensis in Swiss-Webster mice were studied by scanning electron microscopy. Sporozoites were present in the cecum and colon 2 h post-inoculation (PI) and measured 11.3×2.1 m (9–13.9×2–2.2 m). Sporozoites penetrated epithelial cells with an extended anterior end and were constricted at the site of entry. Asexual generations were found in the cecum and colon epithelial cells. In meronts found at days 3–6 PI, merozoites matured synchronously, were oriented in the same direction, and were arranged in a helical pattern. Such meronts measured 11.3×6.4 m (8–13.7×5–7.4 m) and contained 8–12 meroxoites, which measured 11.9×1.5 m (7.4–15.7×1.3–1.8 m). Meronts which were present at day 7 PI measured 9.5×8.2 m (9–10.5×7–9.5 m) and contained 20–50 small merozoites which budded asynchronously from a central residuum. At days 3–7 PI, parasitized epithelial cells had shorter and fewer or no microvilli. The lumenal plasmalemma of the host cell was often disrupted or absent in cells containing mature meronts and escaping merozoites. At day 6 PI, phagocytic cells appeared on the epithelial surface, some of which were in contact with merozoites. Small foci of exposed basal lamina were present at day 7 PI in areas where cells had sloughed from the epithelium.     

Age dependent normal values of histamine and histamine metabolites in human urine

We collected morning urine samples from normal healthy persons, who had not yet breakfasted, in the age range of 2–61 years and measured urinary excretion of histamine and its metabolites N-methylhistamine and N-methylimidazoleacetic acid. The values obtained (expressed in terms of urinary creatinine excretion), were age dependent up to the age of 12. Thereafter, values stabilized and were no longer are dependent.     

Efficacy of the two-microelectrode voltage clamp technique in crayfish muscle

Crayfish muscle fibres of different dimensions were voltage clamped and white noise current was injected into the fibres at various distances from the voltage clamp current electrode. The clamp current was measured and power spectral densities were calculated. This method revealed the efficacy of the voltage clamp in these fibres. In large fibres (l=1.8–2.0 mm; =100–180m) a space clamp was achieved only for a band width f=40Hz. At a distance of 100m from the clamp electrodes f was 250–500Hz. In fibres of medium size (l=1.0–1.3mm; =60–120m) f was about 80Hz and about 800 Hz at a distance of 100m. In experiments with very small muscle fibres (l=400–600m; =30–50m) f was more than 500Hz. The improvement of the space clamp for the smaller muscle fibres resulted mainly from the reduced total membrane capacity,c _m, of these fibres. The limitations of the space clamp could be derived from the impedance properties of the fibres. The band width of the space clamp correlated with the band width for which the square of the absolute impedance, |Z _p|², of the muscle fibre could be described by a simple RC-model. This correlation was demonstrated in a model circuit.Power density spectra of membrane current fluctuations were measured also. To optimize the resolution of these measurements the contribution of instrumental noise was minimized. The effects of instrumental noise are discussed.This investigation was supported by the Deutsche Forschungs-gemeinschaft     

On the mechanism of β-adrenergic regulation of the Ca channel in the guinea-pig heart

Dose-response relations for the increase in the amplitude of Ca current (I _Ca) on external application of isoprenaline (ISP) and internally applied cyclic AMP (cAMP) or catalytic subunit of cAMP-dependent protein kinase (C subunit) were established in single ventricular cells of the guinea pig. An intracellular dialysis technique was used. The threshold concentration was for ISP 10^–9 M, for cAMP 3 M (pipette concentration to which 10^–5 M 3-isobutyl-1-methylxanthine was added) and for C subunit around 0.4 M (pipette concentration). The concentrations for the half-maximal effect were 3.7×10^–8 M (ISP), 5.0 M (cAMP) and 0.95 M (C subunit) and for the maximum effect 10^–6 M (ISP), 15–20 M (cAMP) and 3–4 M (C subunit). For all three agents the maximum increase in the Ca current density was similar (a factor of 3–4), suggesting that they converge on the same site of the Ca channel. Accordingly, the effects of cAMP and C subunit onI _Ca were non-additive to those of ISP. From these data the relationship both between concentrations of ISP and cAMP and between those of cAMP and active C subunit in terms of their effects onI _Ca could be estimated and were compared with those obtained in broken cell preparations.A competitive inhibitor of phosphorylation, 5-adenylyl-imidodiphosphate (5 mM), greatly reduced the effects of ISP and C subunit onI _Ca. Cell dialysis with 3 mM adenosine-5-(-thio)-triphosphate, which produces a dephosphorylationresistant phosphorylation, markedly potentiated the effects of ISP and cAMP onI _Ca.The results support the hypothesis that phosphorylation of a protein within, or close to, the Ca channel by cAMP-dependent protein kinase is the mechanism of -adrenergic stimulation.This work was supported by the Deutsche Forschungsgemeinschaft, SFB 38 (membranforschung), Projekt G, and H0579/6-2     

Effect of alcohol on perceived exertion in relation to heart rate and blood lactate

Summary The purpose of the study was to determine whether the perception of exertion is affected by alcohol during physical performance and whether altered self-rating of exertion is the result of an altered perception per se or of an altered physical capacity to perform work. Ten healthy men participated. Each subject was his own control and received an alcohol dose corresponding to 1 g · kg^–1 body mass in 40% solution in the experimental session. The exercise test was performed on a cycle ergometer with an initial intensity of 50 W which was increased stepwise by 50 W at 4-min intervals up to near-maximal. The rating of perceived exertion (RPE) did not differ between alcohol and control sessions. Alcohol induced a significant increase in heart rate during exercise at 50 W ( = 8 beats · min^–1) and at 100 W ( = 10 beats · min^–1), while the change at higher intensities was insignificant. The systolic blood pressure and the blood lactate concentration were not significantly changed by alcohol. It is concluded that a moderate dose of alcohol does not alter RPE during physical exercise either per se or secondarily to an altered physical capacity to perform work.     

Characteristics of the transport of oxalate and other ions across rabbit proximal colon

In order to characterize oxalate handling by the P2 segment of the rabbit proximal colon, the fluxes of [¹⁴C]oxalate, ²²Na⁺, and ³⁶Cl^– were measured in vitro using conventional short-circuiting techniques. In standard buffer the proximal colon exhibited net secretion of Na⁺ (–2.31±0.64 equiv cm^–2 h^–1), negligible net Cl^– transport, and net secretion of oxalate (–12.7±1.6 pmol cm^–2 h^–1). Replacement of buffer Na⁺ or Cl^– abolished net oxalate secretion, while HCO ₃ ^– -free media revealed a net absorption of oxalate (19.3±4.2 pmol cm^–2 h^–1) and stimulated NaCl absorption. Mucosal amiloride and dimethylamiloride (1 mM) significantly reduced the unidirectional fluxes of oxalate and enhanced sodium secretion by decreasing J _ms ^Na . The anion exchange inhibitor 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS; 0.1 mM, both sides) reduced the unidirectional fluxes of oxalate and chloride. Serosal epinephrine (50 M) stimulated oxalate absorption (21.3±6.3 pmol cm^–2 h^–1) and sodium absorption (5.71±1.20 equiv cm^–2 h^–1), whereas dibutyryl-cAMP enhanced oxalate secretion (–43.4±6.9 pmol cm^–2 h^–1) and stimulated chloride secretion (–7.27 ±0.64 equiv cm^–2 h^–1). These results indicate that the P2 segment of the proximal colon possesses (a) secretory as well as absorptive capacities, (b) oxalate fluxes that are mediated by pathways involving Na⁺, Cl^–, HCO ₃ ^– transport and (c) a net oxalate flux that is sensitive to absorptive and secretory stimuli.     

The role of interoceptors in the regulation of oxygen saturation of arterial blood

Summary Studies were made of the oxygen saturation in arterial blood in animals during exposure to 7500 m in a chamber. The study was carried out after the photoelectrical method by means of continous oxyhemometry in rabbits and cats with denervation of carotid sinus zones, as well as in controls. In the controls the saturation diminished, to 55–62% and increased somewhat after 8–10 minutes' exposition to altitude. In the experimental animals the diminution of oxygen saturation was more pronounced, reaching 40–50% and remained within this range during the whole period of exposure.The experiments demonstrated that the dynamics and the degree of oxygen saturation of arterial blood in case of hypoxia depend on the function of the carotid sinus zones.Presented by Active Member of the Academy of Medical Sciences USSR V. N. Chernigovsky     

Myofibril and sarcoplasmic reticulum changes with exercise and growth

Summary The intent of this study was to observe the effects of different treadmill running programs upon selected biochemical properties of soleus muscle from young rats. Young 10 day litter-mates were assigned to endurance (E), sprint (S) and control (C) groups. Each was partitioned into either 21 or 51 day exercising groups and 10 day controls. For C the myofibril ATPase activity at 21 and 51 days were lower than 10 day activity (p0.05). In the 51 day E group ATPase activity (0.378±0.009 mol Pi·mg^–1·min^–1) was greater than at 10 and 21 days (0.307±0.006 and 0.323±0.008 mol Pi·mg^–1·min^–1) (p0.05). No change occurred in the S group from 10 to 21 and 51 days (p0.05). Both the 21 and 51 day S (0.318±0.011 and 0.399±0.010 mol Pi·mg^–1·min^–1) and E (0.323±0.008 and 0.378±0.009 mol Pi·mg^–1·min^–1) groups had higher activity compared to the C group (0.193±0.029 and 0.172±0.031 mol Pi·mg^–1·min^–1) (p0.05). Maturation (10–51 day) resulted in a lowered sarcoplasmic reticulum (SR) yield and Ca²⁺ binding (p0.05) while Ca²⁺ uptake ability did not change (p0.05). SR yield, Ca²⁺ binding and uptake were not altered with S training (p0.05). The E training resulted in greater Ca²⁺ uptake at 51 days compared to C and S (p0.05), with no change in Ca²⁺ binding (p0.05). The data suggest that E training alters the normal development pattern of young rat soleus muscle.Supported by grants A-6449 and A-0425 from the Natural Sciences and Engineering Research Council of Canada     

Interpretive criteria and quality control for antimicrobial susceptibility tests of levofloxacin

To confirm preliminary interpretive breakpoints for prototype 5 µg levofloxacin disks, 490 strains were tested in vitro using commercially manufactured disks. For in vitro susceptibility testing, 5 µg levofloxacin disks can be used with interpretive criteria of 12 mm for resistant (MIC 8.0 µg/ml) and 16 mm for susceptible (MIC 2.0 µg/ml). Proposed quality control limits for tests of levofloxacin are as follows:Escherichia coli ATCC 25922, zones 29–37 mm or MIC 0.008–0.03 µg/ml;Pseudomonas aeruginosa ATCC 27853, zones 19–26 mm or MIC 0.5–2.0 µg/ml;Staphylococcus aureus ATCC 25923, zones 24–31 mm;Staphylococcus aureus ATCC 29213, MIC 0.06–0.25 µg/ml andEnterococcus faecalis ATCC 29212, MIC 0.25–2.0 µg/ml.     

A pharmacologic study on the histamine releasing effect of atracurium and other muscle relaxants in rat isolated ileum

In this study, the effects of histamine, antihistamines (terfenadine and mepyramine), 5-hydroxytryptamine, and muscle relaxants, atracurium, vecuronium and gallamine, on the tone and contractility of rat ileum were studied and compared in vitro.The aim of the present investigation was to measure, pharmacologically, the histamine releasing effect of muscle relaxants, e.g. atracurium, vecuronium and gallamine, by comparing their contractile response in the absence and presence of antihistamines and comparing their mechanical responses with those produced by histamine and 5-hydroxytryptamine (5-HT).The results showed that the antihistamines, triludan (terfenadine) and mepyramine produced opposite effects in rat ileum. Terfenadine (0.1–20 M) produced concentration-dependent contractions in the rat ileum, whereas mepyramine (0.1–10 M) relaxed the muscle, e.g. by 1.2 g tension. Atracurium (0.5–500 M), vecuronium (0.2–200 M), and gallamine (0.1–7.0 M) produced marked contractions (1.5–4.0 g tension) in rat ileum, and these contractions were markedly reduced by mepyramine (1.3 M) or terfenadine (5 M), implicating histamine release in the generation of these contractions. However, there was some residual contraction which was not blocked by mepyramine, but by 5-HT antagonist, methysergide (1 M), indicating that a mechanism other than histamine release may be responsible for the residual contraction, i.e. release of other mediators such as 5-HT, prostaglandins, or calcium. 5-HT (0.5–500 M) and histamine (0.5–500 M) produced contractions in the rat ileum, but 5-HT was more effective than histamine in producing these contractions. Similarly, gall amine was more effective than atracurium and vecuronium in contracting the rat ileum. Since very high concentrations of muscle relaxants were used, it is suggested that in clinical concentrations, the histamine releasing effect of muscle relaxants was minimal, except that of gallamine, which may release histamine event at very low concentrations. The results are discussed in terms of pharmacologic and immunologic implications of drug reactions at the rat intestinal smooth muscle.     

Temperament as a potential predictor of mortality: Evidence from a 41-year prospective study

Psychological factors were hypothesized to influence mortality, in particular, early versus later mortality. To explore the relationship between temperament, a psychological factor, and mortality in a prospective study of 1337 medical students, we constructed a measure portraying three temperament types, using latent class analysis. Death occurred in 113 subjects over 25–41 years of follow-up. In univariate survival analysis, subjects tending to direct tension inward when under stress (Tension-In) had a higher risk of mortality than Tension-Out or Stable types. These associations persisted after adjustment for age, smoking, cholesterol level, and Quetelet Index. The relative risk (RR) of mortality for Tension-In was 1.56 (95% confidence interval, 1.00–2.44) compared with the Stable group. The risk was due entirely to the excess risk in persons under 55 years of age (RR, 2.59; 95% confidence interval, 1.46–4.62); the corresponding risk of death in older persons was 0.66 (0.30–1.48). Thus temperament is a significant risk factor for mortality, in particular, premature death.     

Mécanismes de l'excrétion d'acide urique chez le rat

Résumé L'excrétion rénale de l'acide urique a été étudiée chez le rat éveillé par des mesures de clearance, à différents taux plasmatiques d'acide urique et dans différentes conditions de débit et de pH urinaires.Le taux plasmatique d'acide urique a été augmenté par une injection initiale soit i.v., soit i.v. et i.p., suivie d'une perfusion i.v. d'acide urique dissous dans du THAM.Au taux plasmatique d'acide urique d'un rat normal (0,6–1,5 mg-%), 16% seulement de la quantité d'acide urique filtrée est excrétée, preuve d'une réabsorption tubulaire importante. Avec l'augmentation du taux plasmatique, ce pourcentage augmente, sans dépasser 100 aux taux plasmatiques atteints (15–20 mg-%), et ceci quelles que soient les conditions expérimentales choisies (diurèse osmotique, abaissement opératoire de la filtration glomérulaire).Une excrétion d'acide urique persistante, aux taux plasmatiques très bas et inférieurs au seuil d'apparition extrapolé suggère l'existence d'un mécanisme de sécrétion tubulaire d'acide urique concommittant.Deux souches de rats de type Wistar se distinguent quant à l'excrétion d'acide urique.

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Mechanisms of the renal excretion of uric acid in the rat

Summary The renal excretion of uric acid was studied in unanesthetized rats by clearance methods at different levels of plasma concentrations, of urine flow and of urinary pH. The plasma concentrations were increased by priming the animal either i.v., or i.v. and i.p., and by infusing uric acid.At physiological plasma levels (0.6–1.5 mg-%), only 16% of the filtered amount of uric acid was excreted. Thus, uric acid was extensively reabsorbed. When the plasma levels were increased up to 15–20 mg-% the fraction of the filtered amount excreted in the urine increased, but never exceeded 100%, even in animals subjected to a decrease of GFR by constriction of the aorta and to mannitol diuresis.Tubular secretion of uric acid in the rat was suggested by the persistence of urinary excretion at very low plasma levels.A difference between two strains of rats with respect to renal uric acid excretion was observed.

Les travaux ont bénéficié du soutien financier du Fonds National Suisse de la Recherche Scientifique (Crédits no. 49833 et 34468).     

Effects of GTPγS and fMet-Leu-Phe on rat PMN phospholipase C (PLC) activity

The PLC activities associated with the cytosol and plasma membrane subcellular fractions of rat PMN were tested for sensitivity to stimulation by GTPS and/or fMet-Leu-Phe. PMN plasma membrane PLC was stimulated 10–20% by 50 M GTPS (p<0.02). fMet-Leu-Phe alone had no effect on the plasma membrane PLC activity, but addition of fMet-Leu-Phe and GTPS together stimulated PLC activity by 20–30% (p<0.05). Neither GTPS nor fMet-Leu-Phe had any significant effect on the cytosolic PLC activity. These data demonstrate the presence of a PLC activity in rat PMN plasma membranes that is sensitive to stimulation by GTPS and fMet-Leu-Phe.