Browsing by Author "CORTHORN, J"

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    EFFECT OF AMILORIDE ON URINARY AND RENAL KALLIKREIN IN THE RAT
    (1986) CROXATTO, HR; CORTHORN, J; ROBLERO, J; VILLALON, P; PEREZ, F
    A single intraperitoneal injection of amiloride in the range of 2.7, 5.4, 10.9, and 21 .mu.mol/100 g body wt in female adult rats produced, in the two successive periods of 4 h following its administration, a significant decrease in the urinary excretory rate of kallikrein. Amiloride, 10.9 .mu.mol/100 g body wt, which significantly reduced active kallikrein, also decreased, but less significantly, the trypsin-activated kallikrein in the urine. The fall in the excretory rate of kallikrein cannot be explained by its enzymatic inhibition by amiloride, since the inhibition was only present at higher concentrations. In hyperhydrated rats amiloride did not change the kallikrein excretory rate in the urine collected within 4 h after the injection. Rats simultaneously injected with 7.6 .mu.mol/100 g body wt furosemide and 10.9 .mu.mol/100 g body wt amiloride excreted levels of kallikrein similar to those found in rats injected with furosemide alone. The kidneys of rats removed after 4 h of administration 10.9 .mu.mol/100 g body wt amiloride showed a significant lowering of the kallikrein activity compared with the respective controls. The decrease of renal kallikrein tended to be similarly pronounced in those rats that received amiloride and furosemide simultaneously. These results confirm the depressive effect of amiloride on kallikrein excretion, which may be explained by an inhibitory action on kallikrein release, activation, and synthesis by the renal cells.
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    ESTERASE-ACTIVITY IN RENIN AND KALLIKREIN EXTRACTS OBTAINED FROM RAT KIDNEYS
    (1975) PORCELLI, G; MARINIBETTOLO, GB; CROXATTO, HR; CORTHORN, J; TEMPESTA, G
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    INHIBITORY EFFECT OF RENIN EXTRACTS UPON URINARY KALLIKREIN EXCRETION
    (1978) CROXATTO, HR; ROJAS, M; CORTHORN, J; ALBERTINI, R; ROBLERO, J
    I.p. injections of 1-5 IU of renin purified extracts, obtained either from hog or rat kidneys, in hyperhydrated rats receiving distilled water or 0.4% NaCl (5% body wt) produce not only a striking increase in the Na excretion rate but a very significant decrease in kallikrein excretion as well. In the urine excreted in the 1st h after renin administration kallikrein practically disappeared in the urine; with higher doses the inhibitory effect was very marked and lasted up to 120 min. In the same rats under a 2nd hyperhydration, not associated with renin injection, kallikrein tends to return to control levels.
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    KALLIKREIN-LIKE ACTIVITY IN PERFUSATES AND URINE OF ISOLATED RAT KIDNEYS
    (1976) ROBLERO, J; CROXATTO, H; GARCIA, R; CORTHORN, J; DEVITO, E
    In the perfusate and the urine produced during perfusion of isolated rat kidneys a kallikrein-like enzyme similar to that found in the kidneys was detectable by bioassay 15-25 min after the beginning of the perfusion. The source of the kallikrein activity was the kidney itself, since before the perfusion was started the blood remaining in the kidneys was washed out, and the perfusion medium was free of kallikrein and its precursors and substrates. The kallikreinlike activity of the perfusate was characterized by an oxytocic effect on isolated rat uterus, a kininogenase activity on kininogen II, an esterase activity on N-benzoyl-L-arginine ethyl ester and a hypotensive effect on anesthetized rats. These properties were inhibited by diisopropyl fluorophosphate and aprotinin but not by pepstatin. Kallikreinlike activity in the perfused kidney was lower than that in the nonperfused organ, but the total amount of kallikrein activity released to the excreted urine and the perfusate was significantly greater than the corresponding activity that disappeared in the kidney. This result agrees with the concept that the renal tissue can synthesize kallikrein.
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    PLACENTAL ALTERATIONS AND INTRAUTERINE GROWTH-RETARDATION ASSOCIATED WITH ENALAPRIL EXPOSURE IN EARLY, MID, AND LATE PREGNANCY IN THE RAT
    (1993) VALDES, G; CHUAQUI, R; CORTHORN, J; DUARTE, I
    Objective: To identify the stage of placental development in which enalapril use in the pregnant rat is deleterious.
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    RELEASE OF ACTIVATABLE KALLIKREIN BY ISOLATED RAT KIDNEYS
    (1981) CORTHORN, J; ROBLERO, J
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    UTERINE KALLIKREIN IN THE EARLY PREGNANT RAT
    (OXFORD UNIV PRESS INC, 1993) VALDES, G; CORTHORN, J; SCICLI, AG; GAETE, V; SOTO, J; ORTIZ, ME; FORADORI, A; SAED, GM
    Uterine homogenates of cycling and early pregnant Sprague Dawley rats and purified rat urinary kallikrein showed similar curves of displacement of I-125-kallikrein binding to a polyclonal antibody. Uterine kallikrein concentration measured by RIA was 8.7 +/- 2 SEM ng/g wet weight during the cycle (n = 6 in diestrus and metestrus) and 20.8 +/- 2 SEM (n = 7) ng/g wet weight on Day 7 of pregnancy (P7) (p < 0.001). On P7, kallikrein concentration was increased 12.4-fold in the implantation nodes, as compared to the interimplantation segments. Uterine homogenates of rats on P7, submitted to DEAE-cellulose chromatography and Sephadex gel filtration, yielded two fractions containing kallikrein immunoreactivity and kininogenase activity, with molecular masses that ranged from 120-125 kDa and 39-43 kDa, respectively. In the RIA, both fractions displayed parallelism with purified kallikrein. Enzymatic activity was expressed after activation by trypsin. It was inhibited by aprotinin, PMSF, p-amino-benzamidine, and leupeptin, but not by soybean or ovomucoid trypsin inhibitors. Kallikrein mRNA was demonstrated by reverse transcriptase/polymerase chain reaction in uteri of nonpregnant and P7 rats. These results show that rat uterus synthesizes one or more serine proteases that are immunologically and enzymatically related to tissue kallikrein. The increase of kallikrein in the implantation node on P7-determined both by an increment of whole uterus kallikrein content and a depletion of the interimplantation segments-suggests that kallikrein may play a role in the vasoactive changes of implantation.
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    VARIATIONS IN UTERINE KALLIKREIN DURING CYCLE AND EARLY-PREGNANCY IN THE RAT
    (OXFORD UNIV PRESS INC, 1994) CORTHORN, J; VALDES, G
    We have previously demonstrated the presence of tissue kallikrein and its mRNA in rat uterus, and an increase of the immunoreactive enzyme on Day 7 of gestation, which suggests a hormonal regulation and a role in implantation. This study pursued the sequential variations during the cycle and early pregnancy. During the estrous cycle, immunoreactive uterine kallikrein levels showed a recurrent pattern, with the highest value on proestrus (12.9 +/- 1.5 ng/uterus or 0.49 +/- 0.03 ng/mg protein), and the lowest on metestrus (4.1 ng +/- 0.5 ng or 0.30 +/- 0.03 ng/mg protein); p < 0.05. During gestation, values on Day 1 (6.1 +/- 0.4 ng/uterus or 0.30 +/- 0.01 ng/mg protein) and Day 3 (4.9 +/- 0.3 ng or 0.35 +/- 0.01 ng/mg protein) were similar to levels during estrus and diestrus; a progressive rise, observed from Day 5 (8.2 +/- 1.1 ng or 0.43 +/- 0.02 ngl mg protein), attained the highest value on Day 7 (15.8 +/- 1.7 ng or 0.78 +/- 0.05 ng/mg protein); p < 0.05. The variations observed during the cycle and early gestation coincide with those described for ovarian steroids and uterine vasoactive changes, suggest the hormonal regulation of uterine kallikrein levels, and support its role in implantation.