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J Genest

Publications and source records attributed to J Genest.

At least 271 records · Page 15Linked to original sources
PubMed1982

Corticotropin-releasing activity of alpha-melanotropin.

Synthetic alpha-melanotropin stimulated the release of immunoreactive adrenocorticotropin from primary cultures of rat anterior pituitary cells. The effect of the alpha-melanotropin was dose-dependent. Cells incubated with synthetic arginine-vasopressin and alpha-melanotropin simultaneously produced an amount of adrenocorticotropin that was greater than the sum of the amount that the cells produced in response to each peptide added separately. Other peptides structurally similar to alpha-melanotropin, such as, beta-, gamma 1-, gamma 2-, and gamma 3-melanotropin, were also tested for adrenocorticotropin-releasing activity. Only the gamma 3-melanotropin demonstrated a statistically significant effect. A vasopressin preparation (Pitressin, Parke-Davis) purified from posterior pituitaries and previously shown to contain some alpha-melanotropin was much more potent in releasing adrenocorticotropin than the synthetic vasopressin.

Adrenocorticotropic Hormone↗
PubMed1982

Synthesis and migration of proteins and glycoproteins in juxtaglomerular cells of sodium-deficient rats. An ultrastructural radioautographic study.

Sections of juxtaglomerular cells from sodium-deficient rats were subjected to radioautography after a single intravenous injection of L-tyrosine-3,5 3H or of L-fucose 3H to identify the sites of synthesis and to follow the migration of newly-formed proteins and glycoproteins. As early as 2 min after injection of L-tyrosine 3H, the label was highest in the rough endoplasmic reticulum (RER), suggesting that cisternal ribosomes are sites of protein synthesis. By 60 min, much of the label had migrated from the RER to the Golgi complex. Some radioactivity was already present over specific granules by 2 min but a peak was reached at 4 h. The label over myofilaments was evident at all time intervals, indicating a certain incorporation of tyrosine into their contractile and/or structural proteins. The label over the cell surface peaked at 4 h. After injection of L-fucose 3H, there was an early and important relative specific radioactivity in the Golgi complex at 5 min with a peak at 20 min and a decrease thereafter. The label increased slightly but steadily in secretory granules and cell surface to reach maxima at 4 h. A low level of radioactivity was recorded in mitochondria at all time intervals. After injection of both fucose 3H and tyrosine 3H, the label was detected at relatively low levels in the cytosol. These results suggest that renin, as the major secretory glycoprotein of juxtaglomerular cells, is synthetized in the RER, packaged in the Golgi complex and found relatively rapidly in newly-formed secretory granules. Part of the fucose and tyrosine labels is also associated with the thick cell coat of these cells.

Animals↗
PubMed1982

Immunohistochemical localization of tonin in rat salivary glands and kidney.

Tonin has been localized in salivary glands and kidney by the indirect immunofluorescence technique of Coons and by the unlabeled antibody technique of Sternberger. Both techniques gave identical results. Immunoreactive tonin was localized in the cytoplasm of granular convoluted tubular cells and on the apical surface of striated duct cells and collecting duct cells of the submandibular gland. In the parotid and sublingual glands, which lack granular cells, tonin was only found on the apical surface of striated duct and collecting duct cells. In the kidney, immunoreactive tonin was found only associated with cells of the distal convoluted tubules. After fixation with Bouin fluid or with ethanol, tonin was found not only on the apical surface of the cells but also in the apical and perinuclear cytoplasm. This cytoplasmic staining has been attributed to artefactual diffusion since, after fixation with formol-picric acid, the enzyme could only be localized on the apical surface of the tubular cells.

Aging↗
PubMed1982

Effect of angiotensin ii and norepinephrine on release of prostaglandins E2 and I2 by the perfused rat mesenteric artery.

Prostaglandin E2 (PGE2) and 6 keto-PGF1 alpha, the stable metabolite of prostacyclin (PGI2), have been measured in the effluent of perfused rat mesenteric arteries by the use of a sensitive and specific radioimmunoassay (RIA) method. The PGE2 and 6 keto-PGF1 alpha were continuously released by the unstimulated mesenteric artery over a period of 145 min. After 100 min of perfusion the release of PGE2 and 6 keto-PGF1 alpha was 45.1 +/- 8.4 pg/min and 254 +/- 75 pg/min respectively, which is in accord with the general belief that PGI2 is the major PG synthesized by arterial tissue. Angiotensin II (AII) (5 ng/ml) induced an increase of PGE2 and 6 keto-PGF1 alpha release without changing the perfusion pressure. The effect of norepinephrine (NE) injections on release of PGs depended on the duration of the stabilization period. The changes of perfusion pressure induced by NE were not related to changes in release of PGs. Thus, it seems that the increase of PG release induced by AII and NE was due to a direct effect of the drugs on the vascular wall. This may represent an important modulating mechanism in the regulation of vascular tone.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Tonin as activator of renin.

Tonin, a new serine protease, found in high concentration in rat submaxillary glands, leads to a significant activation of human amniotic fluid renin. The optimum pH on renin activation by tonin was found at pH 6.0. The reaction was time dependent and the initial rate of angiotensin I generation was constant up to 2 h. The two amniontic fluid samples studied showed an increase in renin activity after incubation with tonin to about five times the control level (268 to 1240 pmol x h-1 x mL-1 and 1490 to 7480 pmol x h-1 x mL-1).

Amniotic Fluid↗
PubMed1982

Mechanism of captopril-induced drinking.

Captopril (SQ 14,225), an orally active angiotensin I-converting enzyme (ACE) inhibitor, increased drinking and produced water diuresis in rats when given orally at a dose of 100 mg.kg-1.day-1. Chronic intraperitoneal infusion of angiotensin (ANG) II or the ANG II antagonist [Sar1, Ile8]ANG II abolished this response. Intracerebroventricular (icv) captopril infused chronically reduced the dipsogenic response to oral captopril. [Sar1, Ile8]ANG II (icv) was without effect on captopril-induced drinking. These results suggest that drinking produced by chronic oral treatment of rats with captopril may be caused by the effects of the elevated ANG I concentrations achieved after blockade of ACE and stimulation of renin secretion by captopril. Systemic ANG II may reduce this response by decreasing renin secretion. Systemic [Sar1, Ile8]ANG II presumably blocks brain ANG receptors for blood-borne ANG. Since icv [Sar1, Ile8]ANG II is ineffective, the receptors for systemic and icv ANG appear to be distinct. Orally administered captopril does not diffuse into the brain.

Angiotensin II↗
PubMed1982

Biochemical and immunological characterization of ectopic tumoral renin.

Biochemical and immunological characteristics of renin secreted by two malignant renin-secreting tumors [pulmonary (PT) and paraovarian (POT)] were studied. They both contain inactive renin (IR), as renin activity of tumoral extracts was able to be increased after acid activation or trypsin treatment (10.1 to 20.8 Goldblatt units/g tissue for PT and 1.4 to 3.71 for POT). Renin activity after activation reached the value obtained by direct RIA of human renin (23 and 3.4, respectively), as both forms are recognized by renin antiserum. Both enzymatic activities could be completely inhibited by renin antiserum. Displacement curves for the two tumoral renins paralleled the MRC renin in the direct RIA. After chromatography on affigel blue, active renin was not bound to the gel, and inactive renin eluted only with 1 M NaCl. On pepstatin A Sepharose and CBL-pepstatin Sepharose (an N-modified-pepstatin), a separation of the two forms of pulmonary renin was obtained; inactive renin eluted with breakthrough proteins, whereas active renin was strongly bound to the gel. After this affinity chromatography, the molecular weights of inactive and active renin, determined on Ultrogel, were very close (46,000 and 42,500). We conclude that 1) ectopic renin in these cases in similar to the renal enzyme; 2) renin can be secreted in an inactive form, supporting the hypothesis of an inactive initial state of renin; and 3) molecular weight differences between the two forms are very slight.

Adenocarcinoma↗
PubMed1982

Radioimmunoassay of corticotropin from plasma.

We describe a specific and highly sensitive radioimmunoassay for corticotropin (ACTH) in human plasma. As little as 1.9 pg of circulating ACTH can be detected per milliliter (0.44 pmol/L). ACTH is first extracted from plasma samples by adsorption onto pretreated Vycor glass powder, eluted from the adsorbent by acetone, and then lyophilized. For purification of 125I-labeled ACTH, a small octadecasilyl silica column is used. The mean (and SD) concentration of ACTH in plasma from 18 ostensibly normal subjects was 10.3 (4.3) pmol/L. After overnight suppression with dexamethasone in seven of these normal subjects, their ACTH values fell to 2.62 (1.3) pmol/L (p less than 0.0005). This assay will permit clinical evaluation of ACTH plasma concentrations in clinical investigation and of the effects of drug administration on circulating ACTH.

Adrenocorticotropic Hormone↗
PubMed1982

Primary hyperaldosteronism: a pituitary--adrenal dysfunction related to a new pituitary glycopeptide?

A novel glycopeptide has been isolated from human and porcine pituitary glands. This substance is the amino-terminal fragment of pro-opiomelanocortin (POMC). The complete amino acid sequence has been determined. When tested for its steroid stimulating activity on an aldosterone secreting human adrenocortical adenoma, it was found to be more potent than angiotensin and ACTH. These results raise the interesting possibility that primary hyperaldosteronism could be related to a pituitary adrenal dysfunction.

Adenoma↗
PubMed1981

Tonin, an esteroprotease from rat submaxillary glands.

Tonin is an enzyme found in the rat submaxillary glands which liberates angiotensin II from angiotensinogen, the Skeggs tetradecapeptide renin substrate, and angiotensin I. Tonin hydrolyzes benzoyl-arginine ethyl ester, benzoyl-arginine methyl ester, tosyl-arginine methyl ester, benzoyl-arginine p-nitroanilide and other small synthetic substrates at an optimum ph of 9.0. Tonin shows, however, a great specificity with respect to angiotensin I. Tonin is inhibited by diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride at high concentrations (greater than 10(-2) M) and by soybean trypsin inhibitor and aprotinin. Tonin is thus an esteroprotease of the class of the serine protease with trypsin- and chymotrypsin-like activity. Tonin belongs to the same family of enzyme as glandular kallikrein and the gamma subunit of the nerve growth factor.

Angiotensin I↗
PubMed1981

Thirst in the rat after ligation of the inferior vena cava: role of angiotensin II.

The role of angiotensin II in thirst states after ligation of the inferior vena cava above (CLA) or below (CLB) the origin of the renal veins as compared to sham operated controls was evaluated 24 hrs after ligation. Water intake was enhanced in CLB rats and even more so in CLA rats. Plasma angiotensin II and urea concentrations and serum osmolality were increased in CLA rats. Plasma sodium concentration and hematocrit were reduced in CLA rats, and hematocrit in CLB rats as well. Water intake in CLA rats was retarded by IV infusions of saralasin. Saralasin infusions in CLA rats resulted in a dramatic increase of plasma angiotensin II concentrations. Ligation of the inferior vena cava induces major changes in body fluid homeostasis, which are more pronounced in CLA than in CLB rats. The increase in water intake in CLA rats appears to be partly mediated by angiotensin II.

Angiotensin II↗
PubMed1981

Activation of renin in an anaplastic pulmonary adenocarcinoma.

1. Biochemical characteristics of a renin-like enzyme secreted by a pulmonary adenocarcinoma have been studied. A very high renin content was revealed by both enzymatic (10.4 Goldblatt units/g of tissue) and direct radioimmunoassay of immunoreactive renin (23 Goldblatt units/g of tissue). 2. The higher value by direct radioimmunoassay suggested the presence of an inactive form of the enzyme. Indeed 40--100% activation occurred with treatment by trypsin or pepsin or prolonged dialysis at pH 7.4 with or without prior acid dialysis. This neutral activation was completely abolished by a serine proteinase inhibitor. 3. A large fraction of the renin in this tumour is inactive. In comparison with other prohormones produced in tumours the findings support strongly the proposition that renin passes through a proenzyme step in synthesis.

Adenocarcinoma↗
PubMed1981

Formation of angiotensin II by tonin from partially purified human angiotensinogen.

The renin substrate (angiotensinogen) has been purified from outdated human blood bank plasma. A 100-fold purification was achieved by ammonium sulphate protein fractionation and four successive chromatographic procedures. We show that tonin, a serine protease enzyme found in submaxillary glands of the rat, cleaves the human plasma angiotensinogen, devoid of tonin inhibiting factor(s), at a pH optimum of 5--5.5. It generates a pressor substance that was identified as angiotensin (A) II. The rate of cleavage of the human angiotensinogen preparation by 1 nmol of renin or tonin was calculated to be 1320 nmol AI/h for renin and 26 nmol AII/h for tonin.

Angiotensin II↗