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Biomedical subjects

R Franco-Saenz

Publications and source records attributed to R Franco-Saenz.

At least 73 records · Page 4Linked to original sources
PubMed1981

In vivo distribution of radioiodinated ACTH1-24 in the rat.

After intravenous injection of 125I-ACTH1-24 into rats, the highest concentration of 125I was found in kidneys, adrenal and liver. Addition of 5- and 30-fold excess unlabelled ACTH reduced the uptake of 125I by 50 and 68%, respectively, indicating that the adrenal uptake was specific. Pretreatment with dexamethasone decreased the adrenal uptake of 125I and caused adrenal atrophy. Chronic ACTH treatment increased the size of the adrenals, but did not affect the adrenal uptake of 125I. These experiments demonstrate selective uptake of 125I by the adrenals after administration of 125I-ACTH1-24.

Adrenal Glands↗
PubMed1981

Effects of beta-lipotropin and beta-lipotropin-derived peptides on aldosterone production in the rat adrenal gland.

To investigate the role of non-ACTH pituitary peptides on steroidogenesis, we studied the effects of synthetic beta-lipotropin, beta-melanotropin, and beta-endorphin on aldosterone and corticosterone stimulation using rat adrenal collagenase-dispersed capsular and decapsular cells. beta-lipotropin induced a significant aldosterone stimulation in a dose-dependent fashion (10 nM-1 muM). beta-endorphin, which is the carboxyterminal fragment of beta-lipotropin, did not stimulate aldosterone production at the doses used (3 nM-6 muM). beta-melanotropin, which is the middle fragment of beta-lipotropin, showed comparable effects on aldosterone stimulation. beta-lipotropin and beta-melanotropin did not affect corticosterone production in decapsular cells. Although ACTH(1-24) caused a significant increase in cyclic AMP production in capsular cells in a dose-dependent fashion (1 nM-1 muM), beta-lipotropin and beta-melanotropin did not induce an increase in cyclic AMP production at the doses used (1 nM-1 muM). The beta-melanotropin analogue (glycine[Gly](10)-beta-melanotropin) inhibited aldosterone production induced by beta-lipotropin or beta-melanotropin, but did not inhibit aldosterone production induced by ACTH(1-24) or angiotensin II. Corticotropin-inhibiting peptide (ACTH(7-38)) inhibited not only ACTH(1-24) action but also beta-lipotropin or beta-melanotropin action; however it did not affect angiotensin II-induced aldosterone production. (saralasin [Sar](1); alanine [Ala](8))-Angiotensin II inhibited the actions of beta-lipotropin and beta-melanotropin as well as angiotensin II. These results indicate that (a) beta-lipotropin and beta-melanotropin cause a significant stimulation of aldosterone production in capsular cells, (b) beta-lipotropin and beta-melanotropin have a preferential effect on zona glomerulosa cells, (c) beta-melanotropin contains the active peptide core necessary for aldosterone stimulation, (d) the effects of these peptides on aldosterone production may be independent of cyclic AMP, and (e) the receptors for beta-lipotropin or beta-melanotropin may be different from those for ACTH or angiotensin II.

Adrenal Glands↗
PubMed1981

Effects of rat urinary arginine esterases on rat kidney to release renin.

Urinary kallikrein has been reported to activate human plasma inactive renin. Our previous report suggests that rat urinary kallikrein releases active renin from rat renal cortical slices. Recently, McPartland et al. were able to separate the A esterase activity of male rat urine into two components: A1 and A2. To evaluate whether these other urine arginine esterases release renin from the kidney, esterases A1 and A2 were isolated from male rat urine using DEAE-Sephadex chromatography and superfused to rat renal cortical slices. The renin-stimulating action of these enzymes was compared to that of rat urinary kallikrein. Rat urinary kallikrein stimulated renin release in a dose-dependent fashion between 70--140 milliesterase units (mEU)/ml. Esterase A2 dose stimulated renin release significantly between 120--140 mEU/ml. However, esterase A1 did not stimulate renin release at concentrations between 70--140 mEU/ml. Although Trasylol completely abolished kallikrein and esterase A2 stimulated renin release, soybean trypsin inhibitor blocked only esterase A2-stimulated renin release. The physiological role and site of origin of the A1 and A2 esterases is unknown. However, similar to kallikrein, esterase A2 is a potent stimulator of renin release and may be physiologically important for the release and activation of renin in the kidney.

Animals↗
PubMed1981

The role of renal prostaglandins in the renin response to isoproterenol in the rat in vitro.

Renal prostaglandins (PGs) have been considered to be important mediators of renin release. However, the mechanism and the site of action have not been clarified. To investigate the role of PGs in the control of isoproterenol-induced renin release, we studied the effect of two inhibitors of PG synthesis, indomethacin and meclofenamate, on the renin release stimulated by isoproterenol and dibutyryl cAMP. We used an in vitro superfusion system of rat renal cortical slices. Neither indomethacin nor meclofenamate affected basal renin release. Isoproterenol (8 x 10(-7) M) increased renin and PGE2 release which was blocked by indomethacin (10(-4) M) and meclofenamate (10(-4) M). Dibutyryl cAMP stimulated renin release significantly, and this effect was not blocked by indomethacin (10(-4) M). Moreover, dibutyryl cAMP did not stimulate PGE2 release. In view of the fact that we have previously shown that PG-stimulated renin release is not blocked by propranolol and is enhanced by phosphodiesterase inhibitors, our present experiments suggest that the site of action of PGs on renin release is located between the beta-adrenergic receptor and the generation of cAMP.

Animals↗
PubMed1981

Cortisol production by testicular tumors in a patient with congenital adrenal hyperplasia (21-hydroxylase deficiency).

Bilateral testicular tumors are known to occur in congenital adrenal hyperplasia, but their steroidogenic properties are not well studied. We have recently demonstrated steroid 11 beta-hydroxylase activity in these tumors from a 27-yr-old patient with documented salt-losing congenital hyperplasia (21-hydroxylase deficiency). Spermatic venous blood obtained at operation contained 3.6-5 ng/ml cortisol, as measured by specific RIA after Sephadex LH-20 chromatography. In contrast, the peripheral venous cortisol level was 0.64 ng/ml. The presence of 11 beta-hydroxylase activity was demonstrated by the in vitro conversion of [3H]deoxycorticosterone to [3H]corticosterone in tumor tissue. The conversion ratio of deoxycorticosterone to corticosterone was 4.3% and 7.07%/mg tissue in the tumor tissue, whereas in normal testicular tissue, it was less than 1%. The radiochemical identity of corticosterone was confirmed by rechromatography on Sephadex LH-20, coelution with added [14C]corticosterone, and a constant 3H to 14C ratio after acetylation and thin layer chromatography. The tumor cells grown in primary culture produced steroids and responded to ACTH and hCG. Electron microscopy of the tumor revealed a large number of mitochondria containing electron dense granules. Light microscopy was compatible with Leydig cell tumor. In conclusion, testicular tumors in association with congenital adrenal hyperplasia have morphological features of Leydig cells but have the capability of 11 beta-hydroxylation and cortisol production, properties which are unique to adrenocortical tissue. These findings suggest that they originate from pluripotential cells in the testicles. Regression of these tumors has been reported with optimal biochemical control of the disease.

Adrenal Hyperplasia, Congenital↗
PubMed1981

Active and inactive renin in low renin states: studies in human plasma.

Low PRA and active renin (AR) may be accompanied by low inactive renin (IR), indicating impaired renin production, or by normal or elevated IR, suggesting defective conversion to AR. To explore these possibilities, plasma AR and IR (acid activation method) were measured in normal volunteers and in patients with low PRA. All low renin states showed significant low PRA and AR when compared to normals; on the other hand, IR was 11.8 +/- 1.1 ng/ml.h in normals; low in primary aldosteronism (2.1 +/- 0.5 ng/ml.h) and anephric subjects; normal in low renin essential hypertension (7.5 +/- 1.3 ng/ml.h), nondiabetic hyporeninemic hypoaldosteronism (9.4 +/- 1.6 ng/ml.h) and diabetic hyporeninemic hypoaldosteronism (17.3 +/- 2.5 ng/ml.h); and significantly elevated in diabetics with nephropathy (21.0 +/- 1.6 ng/ml.h). The acute iv infusion of 2 liters saline in normal subjects did not decrease IR (11.8 +/- 2.0 vs. 13.0 +/- 1.8 ng/ml.h) despite a reduction in PRA and AR of 50-75%. These data indicate that in cases of primary aldosteronism and in anephric subjects both AR and IR are decreased, suggesting a decrease in total renal synthesis or release, whereas in low renin essential hypertension, nondiabetic hyporeninemic hypoaldosteronism, diabetic hyporeninemic aldosteronism, and diabetics with nephropathy AR is low and IR is normal or high, suggesting the possibility of impaired conversion to AR.

Adolescent↗
PubMed1980

Effects of beta-lipotropin on aldosterone production in rats.

1. beta-Lipotropin has a potent aldosterone stimulating effect in vitro and in vivo in rats. 2. The maximum aldosterone response to beta-lipotropin was the same as to ACTH and greater than to angiotensin II. 3. Although doses of ACTH which maximally stimulated aldosterone significantly increased cyclic AMP production, maximally stimulating doses of sheep beta-lipotropin did not increase cyclic AMP production significantly. 4. These data suggest that beta-lipotropin may play a role in aldosterone regulation through a mechanism different from that of ACTH.

Adrenal Glands↗
PubMed1980

Direct action of rat urinary kallikrein on rat kidney to release renin.

To study the effect of kallikrein on renal renin release, we superfused rat renal cortical slices with 3.5 to 140 milliesterase units (mEU)/ml of purified rat urinary kallikrein. Kallikrein was a potent stimulus of renin release. Renin rose in a dose-dependent fashion from 70 mEU/ml to 140 mEU/ml. The response to 140 mEU/ml was greater than that seen with maximal doses of prostaglandin E2 (170 +/- 43%, P < 0.05) and at least the same as isoproterenol (242 +/- 49% increase), or dibutyryl cyclic AMP (272 +/- 40%). Trypsin was ineffective under these experimental conditions. Kallikrein-stimulated renin release was completely abolished by trasylol, whereas bradykinin did not increase renin production, indicating that kallikrein's effect is not mediated via kinin generation. There was no demonstrable acid activation or kallikrein activation of the superfusate and chromatography on Sephacryl S-200 revealed a single renin peak of -40,000 mol wt, suggesting that all of the renin release was in the active form. The data suggests that urinary kallikrein acts directly on the rat kidney to release renin, possibly via proteolytic conversion of prorenin to active renin. Our results support the concept that kallikrein may be an endogenous activator of prorenin in the kidney.

Animals↗
PubMed1980

Prostaglandin stimulation of renin release: independence of beta-adrenergic receptor activity and possible mechanism of action.

Using a continuous superfusion system of rat kidney cortical slices, we investigated the renin-releasing effect of prostaglandin E2 (PGE2) and its possible mechanism of action. PGE2 caused significant stimulation of renin release in a dose-dependent fashion at concentrations of 3 x 10(-6) to 10(-4) M. Isoproterenol (8 x 10(-7) M) stimulated renin release significantly, and its effect was completely abolished by propranolol (2 x 10(-5) M). PGE2-stimulated renin release was not blocked by the same dose of propranolol. Dibutyryl cAMP caused a dose-dependent increase in renin release at concentrations of 10(-5) to 5 x 10(-3) M. Theophylline (4 x 10(-3) M) had no effect on renin release, but when added to subthreshold doses of PGE2 (10(-6) M), it stimulated renin release significantly. The simultaneous addition of maximal stimulating doses of PGE2 and dibutyryl cAMP had no additive or synergistic effects. These experiments show that PGE2 causes stimulation of renin release by a direct effect on the JG cell. The renin-releasing effect of PGE2 does not depend upon the beta-adrenergic receptors but may be mediated through cAMP.

Animals↗
PubMed1979

A model for the study of the oral administration of peptide hormones.

The intragastric administration of lysine vasopressin (LVP) to rats is used as a model to study the biological activity of orally administered peptide hormones. Using a modification of the antidiuretic assay of Sawyer, LVP given by stomach tube caused a significant antidiuresis that was dose dependent in doses of 300 to 2000 mU. The simultaneous administration of the protease inhibitor, Trasylol, increased the antidiuretic effect of LVP. The synthetic peptide (1-deamino, 4 valine)-8-D-arginine-vasopressin also caused a dose-dependent prolonged and significant antidiuresis. No pressor effect was observed after intragastric administration of LVP in doses up to 40 U/rat. We are now using this model to test other procedures for enhancing the activity of lysine vasopressin administered in the gastrointestinal tract such as encapsulation into liposomes. The information gained with vasopressin will then be applied to insulin with the ultimate goal of making oral administration practical.

Administration, Oral↗
PubMed1975

Transmembrane potentials and steroidogenesis in normal and neoplastic human adrenocortical tissue.

Trans-membrane potentials and steroidogenesis were measured in superfused slices of non-tumor and neoplastic human adrenocortical tissue. Non-tumor tissue was obtained at the time for renal transplant or from tissue removed along with tumors. Non-tumor human adrenocortical tissue had electrophysiological and steroidogenic properties similar to those of the rat and rabbit. In normal medium ACTH stimulated steroidogenesis but had no effect on the membrane potential. In K+-free medium, the cells hyperpolarized, and subsequent addition of ACTH caused depolarization. Trans-membrane potentials of adrenocortical tumors were lower than those of non-tumor cells. Ommission of K+ from the medium caused hyperpolairzation of the tumor cells, but the trans-membrane potentials did not reach the values of hyperpolarized non-tumor cells. ACTH, added to the K+-free medium, caused little or no change in membrane potential of tumor cells except in one case of a virilizing adenoma, which responded very much like non-tumor tissue. Except for the virilizing adenoma, tumor tissue slices produced little or no detectable fluorogenic steroid, even in the presence of large amounts of ACTH or cyclic AMP. The virilizing adenoma responded with increased steroidogensis to ACTH and cyclic AMP.

Adenoma↗
PubMedDate not supplied

Acetaldehyde inhibits the anti-elastase activity of alpha 1-antitrypsin.

There are genetic and exogenous factors responsible for alpha 1-antitrypsin (alpha 1-AT) deficiency which may lead to cirrhosis of the liver and emphysema. The present study was initiated on a biochemical level in order to determine whether acetaldehyde, the major product of ethanol metabolism, is capable of influencing the physiological effect of alpha 1-AT upon elastase, an enzyme which is capable of inducing emphysema. The effects of acetaldehyde and ethanol upon elastase and alpha 1-AT were tested. Acetaldehyde at 0.3-M and 1.2-M concentrations inhibited the anti-elastase activity of alpha 1-AT. Acetaldehyde at 0.03-M and 0.07-M concentrations did not affect elastase activity and had a slight effect at 0.12-M levels. Equivalent amounts of ethanol were without influence upon elastase activity or alpha 1-AT function. These data provide biochemical support for the possibility that heterozygous males with lower than normal alpha 1-AT levels may be at much higher risk to develop liver disease, emphysema, and alpha 1-AT deficiency as a consequence of chronic exposure to ethanol and concomitant circulating acetaldehyde levels.

Acetaldehyde↗