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J Genest

Publications and source records attributed to J Genest.

At least 289 records · Page 16Linked to original sources
PubMed1981

Purification and partial characterization of a plasma inhibitor of tonin.

A plasma inhibitor of tonin activity in the rat, was purified by ammonium sulfate precipitation, ion-exchange of chromatography, and gel filtration. Its purity was investigated by analytical electrophoresis on polyacrylamide gel and by ultracentrifugation sedimentation velocity. The molecular weight (360 000) of the purified inhibitor was determined by sodium dodecyl sulfate electrophoresis and its isoelectric point (4.5) by gel isoelectrofocusing. The Stokes radius (640 nm) was evaluated by gel filtration studies and a frictional ratio (f/fo) of 1.95 was calculated from the molecular weight and Stokes radius. Kinetic studies using angiotensin I as substrate showed that the inhibition of tonin by the purified inhibitor was noncompetitive and does not exceed 70%. Electrophoresis showed the same mobility for [125I]tonin bound to plasma proteins and for [125I]tonin bound to the purified inhibitor. The inhibitor may be a protein resembling half of the dimeric protease inhibitor rat alpha 1-macroglobulin or human alpha 2-macroglobulin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1981

Renin substrate in rat mesenteric artery.

The concentration of renin substrate (RS) was measured in rat mesenteric artery tissue. The concentration of this substrate both in arterial tissue and in plasma was markedly higher in rats 1 day after bilateral nephrectomy than in sham-operated controls, the percentage difference being higher in plasma than in arterial RS. Conversely, the decrease apparently induced 3 days after adrenalectomy (i.e., the difference in RS concentration from sham-operated rats) was greater in arterial tissue than in plasma. This finding may be explained by changes in RS concentrations induced by the sham operation. Sham surgery itself increased plasma RS after 1 day (but not after 3 days) and arterial RS after 3 days (but not after 1 day). There was a positive correlation between arterial and plasma renin substrate concentration for the overall results but not within individual groups. As renin and angiotensin-converting enzyme activity are also present in arterial tissues, all the necessary components for local generation of angiotensin II have now been shown to be present within the wall of resistance vessels.

Adrenal Glands↗
PubMed1981

Effects of tonin on the response to norepinephrine by the aortic strip of the hypertensive rat.

The response to norepinephrine (NE) of arterial smooth muscle from two types of experimental hypertensive rats was investigated. Aortic strips from one-kidney, one-clip hypertensive animals were less responsive to NE than those from their normotensive controls but strips from one-kidney, one-clip hypertensive animals showed no difference from their corresponding controls. The contractility in response to NE was the same in all groups. These results suggest that the mechanisms responsible for lesser reactivity in the one-kidney hypertensive group are not a consequence of elevated blood pressure itself but may be related to changes in the intrinsic sensitivity of aortic smooth muscle. Tonin potentiated the contraction induced by NE in aortic strips from hypertensive and normotensive rats. This effect was more pronounced in the one-kidney, one-clip hypertensive animals, so that although the aortic smooth muscle from these animals is less reactive to NE, the decreased reactivity can be more than compensated by the presence of tonin. The mechanism of potentiation is not yet clear but the fact that Saralasin did not inhibit it suggests that angiotensin II is not generated in situ.

Animals↗
PubMed1981

Detection from rat pituitary of beta-lipotropin and materials containing opiatelike activity by combined enzymatic radioreceptor assay.

Tonin, a proteolytic enzyme isolated from rat submaxillary gland, was allowed to react upon ovine beta-lipotropin (beta-LPH) at 37 degrees C at a variety of pH values and for different lengths of time. Opiatelike activity generated by the reaction was assessed using a radioreceptor assay for beta-endorphin with rat brain homogenate. [3H]naloxone, and beta-endorphin as receptors, tracer, and hormone standard, respectively. Cleavage of beta-LPH with tonin produced a 10-fold increase in opiatelike activity as compared with beta-LPH alone. Digestion of beta-LPH with other enzymes such as renin, cathepsin D, trypsin, and chymotrypsin produced much less opiatelike activity. beta-Endorphin and methionine-enkephalin were not cleaved by tonin. Using this new assay, we were able to detect beta-LPH and materials containing opiatelike activity from rat pituitary extracts after gel chromatography. It is more specific and more sensitive than trypsin digest.

Animals↗
PubMed1981

Pressor effect of tonin in anephric animals.

Tonin was injected intravenously to normal rats without effect on blood pressure. Twenty-four hours after bilateral nephrectomy, tonin produced a dose-dependent pressor effect in rats which was abolished by the angiotensin antagonist [Sar1-Ala8]-angiotensin II. Vascular response to angiotensin II was slightly increased after nephrectomy. Plasma angiotensin II increased significantly after injection of tonin and disappeared biexponentially with a half-life of less than 1 min for the fast component and 9 min for the slow component. The change in plasma angiotensin II correlated with the elevation in mean blood pressure. No difference in inhibitory power of plasma on tonin activity could be shown between intact and nephrectomized rats. In vitro, the initial velocity of generation of angiotensin II by tonin acting on plasma increased after addition of semipurified rat renin substrate and was significantly greater in plasma of nephrectomized rats. In nephrectomized rabbits, but not in intact ones, a dose-dependent pressor effect was produced by tonin. These data demonstrate the in vivo production of angiotensin II by tonin in an animal model with elevated substrate levels. Together with the in vitro data, these results suggest a role for substrate concentration in the expression of tonin enzymatic activity in vivo.

Angiotensin II↗
PubMed1981

Role of Ca2+ in response of adrenal glomerulosa cells to angiotensin II, ACTH, K+, and ouabain.

The effects of Na+-K+-ATPase inhibition by ouabain and blockage of Ca2+ influx into the cell by verapamil and lanthanum on the response of isolated rat adrenal glomerulosa cells to angiotensin II, ACTH, and K+ were studied. Ouabain significantly increased basal aldosterone output at a concentration of 10(-5) mol/liter, whereas at 10(-3) mol/liter basal secretion was unaffected. Steroidogenic response to angiotensin II was significantly potentiated at concentrations of ouabain of 10(-5) mol/liter, but responses to angiotensin II, ACTH, and K+ were inhibited by 10(-4) and 10(-3) mol/liter of ouabain. The Ca2+ antagonist verapamil (10(-6) to 10(-4) mol/liter) decreased basal aldosterone secretion as well as the response to angiotensin II, ACTH, and K+. The effects of ouabain (10(-5) mol/liter) on basal and stimulated steroidogenesis were abolished by verapamil (10(-4) mol/liter). Lanthanum decreased basal and angiotensin II, ACTH, and K+ induced aldosterone secretion. The effects of ouabain (10(-5) mol/liter) on basal and stimulated aldosterone biosynthesis were blocked by lanthanum. These results suggest that Ca2+ mediates the effects of angiotensin II, ACTH, K+ and Na+-K+-ATPase inhibition on aldosterone biosynthesis. Ca2+ may be the final common intracellular messenger of most aldosterone secretagogues.

Adrenal Glands↗
PubMed1981

Brain receptor binding and central actions of angiotensin analogs in rats.

The possible physiological importance of brain receptors for angiotensin was investigated. Structure-activity relationships were established for 12 fragments and analogs of angiotensin II (ANG II). 1) Affinities of the peptides were determined in an in vitro assay of rat brain angiotensin receptors. 2) Blood pressure (BP) and water intake following intracerebroventricular administration of the peptides to conscious rats were monitored. In vitro, ANG II and [des-Asp1]ANG II displayed the highest affinities. [Trp1]ANG II and [Trp8]ANG II had one-eighth and one-ninth the affinity of ANG II, respectively. Multiple substitutions in positions 1, 4, and 8 produced a 1,000-fold fall in binding affinity. Excellent correlation was found between the in vitro binding affinities and the in vivo central activities of the peptides on BP (r = 0.975) and on water intake (r = 0.900). The results suggest that the biochemically characterized brain angiotensin receptors may be physiologically relevant to BP and body fluid homeostasis. The brain angiotensin receptors mediating BP and thirst have very similar structural requirements.

Angiotensin II↗
PubMed1981

Effect of N-terminal portion of pro-opiomelanocortin on aldosterone release by human adrenal adenoma in vitro.

An adrenal cortex adenoma, surgically removed from a female patient with primary aldosteronism, was used to examine the effect of ACTH, angiotensin II, gamma 3-MSH, and the N-terminal fragment of pro-opiomelanocortin purified from porcine anterior pituitaries on aldosterone release in vitro. Primary cultures of tumor cells were incubated as a monolayer in a 96-well microtitration plate and the aldosterone release was measured in the incubation medium after 2 h of incubation in the presence of absence of different concentrations of the peptides. On a molar basis, the N-terminal portion of pro-opiomelanocortin seems to have the highest activity of all of the peptides assayed.

Adenoma↗
PubMed1981

[Not Available].

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Canada↗
PubMed1981

The extra-adrenal synthesis of epinephrine in rats. Possible involvement of dopamine sulfate.

Bilaterally adrenalectomized rats were administered [3H]L-dopa, [3H]DA, and [3H]DASO4. Both [3H]L-dopa and [3H]DASO4 were found to generate [3H]E in the urine and kidney tissues of adrenalectomized rats, whereas [3H]DA did not produce any detectable [3H]E. [3H]CAs in tissues and urine were analyzed by reverse-phase high-performance liquid chromatography. The identities of the [3H]CAs in the urine were further verified by a double-labeling radioenzymatic technique. The results demonstrated that in the rat E can by synthesized outside the adrenals and that DASO4 can serve as an intermediate in such a synthesis. [3H]DASO4 was also converted to [3H]DA and [3H]NE, indicating that it can be metabolized in vivo and could be the source of free DA in urine.

Adrenal Glands↗
PubMed1980

Effects of intracerebroventricular administration of tonin on water intake and blood pressure in the rat.

Intracerebroventricular administration of tonin, an enzyme which releases angiotensin II directly from various substrates, stimulated water intake and increased blood pressure in the rat. These responses were abolished by the simultaneous administration of an angiotensin II antagonist and were unaffected by the nonapeptide inhibitor of angiotensin I-converting enzyme. These findings suggest that tonin may participate in the physiological regulation of water balance and blood pressure through local and direct generation of angiotensin II in the central nervous system.

Angiotensin II↗
PubMed1980

Effects of tonin on vascular smooth muscle of the hypertensive rat and normal rabbit.

1. The response of arterial smooth muscle to noradrenaline was studied in one-clip hypertensive rats with or without the contralateral/kidney and in normotensive rabbits. 2. Strips of aorta from one-kidney, one-clip hypertensive animals were less responsive to noradrenaline than normotensive control rats. The contractile response of strips from two-kidney, one-clip hypertensive animals was not different from the control group. These results suggest that the mechanisms responsible for the lesser reactivity in the one-kidney hypertensive group are not a consequence of elevated blood pressure itself, but may be related to the intrinsic contractility of aortic smooth muscle. 3. Tonin potentiated the contraction induced by noradrenaline in aortic strips from hypertensive and normotensive rats. However, this effect was more important in the one-kidney, one-clip hypertensive animals. In the aortic and mesenteric strips from normal rabbits, tonin produced not only potentiation to noradrenaline but direct contraction. 4. The potentiation to noradrenaline and the direct effect of tonin were not affected by a variety of antagonists but were blocked by a calcium ion antagonist, verapamil, suggesting that tonin may act directly on vascular smooth muscle through mechanisms which might be mediated by calcium ions.

Animals↗