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Biomedical subjects

F Morel

Publications and source records attributed to F Morel.

At least 199 records · Page 11Linked to original sources
PubMed1983

Changes in tubular basolateral membrane markers after chronic DOCA treatment.

Chronic administration of DOCA to rabbits is known to increase the surface area of the basolateral membrane and the Na-K-ATPase activity of the cortical collecting tubule (CCT). We attempted to ascertain 1) whether Na-K-ATPase is the only basolateral membrane marker induced by DOCA, and 2) whether CCT is the only nephron segment affected by this steroid. We measured the activity of Na-K-ATPase and adenylate cyclase (AC) and the protein content of nephron segments microdissected from control and DOCA-treated rabbits. Morphogenic effects of DOCA, assessed by 30-60% increases in protein content, were specifically observed in the distal convoluted tubule, CCT, and medullary collecting tubule. When expressed as a function of tubular length, Na-K-ATPase activity rose from 80 to 200% in all these segments, whereas the increments in AC of 40-70%, observed in response to four different hormones, occurred only in some of them. When expressed as a function of protein content, Na-K-ATPase activity increased but AC activity remained unchanged. This study indicates that the morphogenic action resulting from chronic DOCA administration affects the entire rabbit distal nephron. During this action Na-K-ATPase is the preferentially induced enzyme.

Adenosine Triphosphatases↗
PubMed1982

Multiple hormonal control of adenylate cyclase in distal segments of the rat kidney.

Using the single tubule adenylate cyclase microassay, we investigated in vitro in three different segments of the rat nephron whether the effects of various hormones are additive when these hormones are tested in combination. In the cortical portion of the thick ascending limb (CAL), no additivity of the effects of glucagon, calcitonin, and PTH was observed. In the medullary portion of the thick ascending limb (MAL), the effects of vasopressin and glucagon were only partly additive, and the effects of vasopressin and calcitonin were fully additive. In the cortical collecting tubule (CCT), the effects of calcitonin and vasopressin were nonadditive in the kidneys in which vasopressin alone induced a high cyclase stimulation, whereas they were fully additive when vasopressin induced a low cyclase stimulation. The data suggest that in each segment, the hormones tested stimulated the same cells: no additivity was observed when cyclase Vmax acted as the limiting factor of the response; partial or full additivity was observed when the number of hormone receptors acted as the limiting factor of the response. As a consequence, calcitonin, glucagon, and PTH should induce the same effects in CAL; vasopressin, glucagon, and calcitonin, the same effects in MAL; and vasopressin and calcitonin, the same effects in CCT.

Adenylyl Cyclases↗
PubMed1981

Distribution of hormone-dependent adenylate cyclase in the nephron and its physiological significance.

In addition to the well established action of PTH in proximal tubules and of AVP in collecting tubules, polypeptide hormones were recently shown to regulate transport properties in other tubular portions. Although still scarce, such physiological studies using isolated perfused tubules demonstrated hormonal effects in those nephron segments observed to contain responsive adenylate cyclase and not in the others. Moreover, the same effects were elicited by applying exogenous cAMP or cAMP derivatives. There is, therefore, good evidence that hormone-dependent adenylate cyclase is involved in the cell mechanisms through which many hormones regulate tubular functions. The effects obtained varied depending on the segment of tubule used. It is not yet established whether the nature of the hormonal effect induced via cAMP is entirely specified by the responding cell types or is also specified by the hormone itself. Further studies are needed to clarify this important problem, as well as many other as yet unsolved questions. There is obviously much more to learn about the hormonal regulation of tubular cell functions by using appropriate biochemical and physiological micromethods.

Adenylyl Cyclases↗
PubMed1981

Sites of hormone action in the mammalian nephron.

Hormone-dependent adenylate cyclase activity was measured separately in the different nephron portions by combining the microdissection of collagenase-treated rabbit kidneys and the use of a single tubule enzyme microassay. The results obtained in the rabbit for vasopressin, parathyroid hormone, calcitonin, and isoproterenol are given and discussed. Each hormone stimulated adenylate cyclase activity in several well-localized segments of tubule according to a highly specific and reproducible pattern. Sharp transitions were generally noted between responsive and unresponsive nephron portions. In the rat kidney, the functional segmentation of the distal convoluted tubule was not as clearly delineated as in the rabbit kidney. Various nephron segments of the rat kidney were observed to contain glucagon-sensitive adenylate cyclase activity. When the results obtained for vasopressin are compared in rabbit, rat, mouse, and human kidneys, species differences are noted with respect to the responsiveness to arginine vasopressin in the medullary portion of thick ascending limbs of Henle's loops. It is concluded that biochemical approaches can be used as a means of investigating problems dealing with kidney physiology very near the cell level.

Adenylyl Cyclases↗
PubMed1981

[Vasopressin action sites along the nephron (author's transl)].

Sites of action of vasopressin along the nephron were investigated by using a microassay for adenylate cyclase for single pieces of tubule microdissected from collagenase-treated kidneys. In the rabbit, not only the medullary and cortical portions of collecting tubules, but also the thin and thick segments of the ascending limb of Henle's loop were observed to contain adenylate cyclase highly responsive to arginine-vasopressin. In contrast, the other segments of the nephron-including the descending limb of the loop, the distal convolution, and the connecting tubule -- were unresponsive to vasopressin. Qualitative and quantitative species difference were noted between rabbit, rat, mouse and man, regarding vasopressin responsiveness in distal tubules and ascending limbs. As an example, adenylate cyclase in thick ascending limb is not sensitive to vasopressin in man whereas, in rat, it is as responsive as the collecting tubule. The physiological relevance of these results is discussed.

Adenylyl Cyclases↗
PubMed1980

The distal nephron of rat kidney: a target site for glucagon.

Glucagon-sensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity was measured in nine different portions of the rat nephron. Each sample contained a single piece of tubule isolated by microdissection from collagenase-treated kidney tissue. As compared to basal activity, 1 microM porcine glucagon stimulated adenylate cyclase 60-fold in the medullary portion and 40-fold in the cortical portion of the thick ascending limb, 23-fold in the early distal convoluted tubule, 11-rold in the cortical collecting tubule, and 8-fold in the medullary collecting tubule. No stimulation was observed in proximaly tubules and thin segments of the loop of Henle. Half-maximal stimulations were obtained with about 10 nM glucagon in the responsive nephron portions.

Adenylyl Cyclases↗
PubMed1980

Adenylate cyclase responsiveness to hormones in various portions of the human nephron.

The action sites for parathyroid hormone (PTH), salmon calcitonin (SCT), and arginine-vasopressin (AVP) were investigated along the human nephron by measuring adenylate cyclase activity, using a single tubule in vitro microassay. Well-localized segments of tubule were isolated by microdissection from five human kidneys unsuitable for transplantation. PTH (10 IU/ml) increased adenylate cyclase activity in the convoluted and the straight proximal tubule, in the medullary and cortical portions of the thick ascending limb, and in the early portion of the distal convoluted tubule (corresponding stimulated:basal activity ratios were 64, 19, 10, 18, and 22, respectively). SCT (10 ng/ml) increased adenylate cyclase activity in the medullary and cortical portions of the thick ascending limb, in the early portion of the distal convoluted tubule, and, to a lesser extent, in the cortical and the medullay collecting tubule (activity ratios were 7, 14, 15, 3, and 3, respectively). AVP (1 microM) stimulated adenylate cyclase activity in the terminal nephron segments only, i.e., the late portion of the distal convoluted tubule, the cortical and medullary portions of the collecting tubule (activity ratios 81, 51, and 97, respectively). As measured in one experiment, nearly one-half maximal responses were obtained with 0.1 IU/ml PTH or 0.3 ng/ml SCT in thick ascending limbs and with 1 nM AVP in collecting tubules, suggesting that enzyme sensitivity to hormones as well preserved under the conditions used in this study.

Adenylyl Cyclases↗
PubMed1979

Hormone-sensitive adenylate cyclase along the nephron of genetically hypophosphatemic mice.

The response of the adenylate cyclase (AC) activity to PTH and calcitonin was measured along the nephron of normal (N) and mutant hypophosphatemic (Hyp) mice of the C 57 BL/6J strain, using in vitro single tubule AC microassay. In each experiment, a Hyp mouse was paired to a N mouse from the same litter. In the presence of PTH (10 U/ml), AC activities (femtomoles cAMP per millimeter of tubule per 30-min incubation) were reduced in the proximal convoluted tubule of Hyp mice as compared to N mice in all experiments (448 +/- (SEM) 46 vs. 831 +/- 79, N = 4, P less than 0.01). Some decrease in AC response to PTH also was noted in the cortical portion of the thick ascending limb of the loop of Henle (476 +/- 70 in Hyp mice vs. 719 +/- 83 in N mice, N = 4, P = NS). The Hyp and N AC responses to PTH were similar in the "bright" and "granular" portions of the distal convoluted tubule (1524 +/- 177 in Hyp mice and 1538 +/- 228 in N mice, N = 4). The other segments tested were not responsive to PTH (except the pars recta of the proximal tubule). In the presence of salmon calcitonin (10 ng/ml), a striking 5- to 12-fold increase in AC activity of the "bright" and "granular" portions of the distal convoluted tubule was observed in each Hyp mouse as compared to its paired N control (2434 +/- 618 vs. 399 +/- 56, N = 6, P less than 0.01). The AC response to calcitonin was also increased, though to a lesser extnet (Hyp/N = 1.8) in the "light" portion of the distal tubule (590 +/- 60 in Hyp and 352 +/- 36 in N mice, P less than 0.01). Other segments of the mouse nephron were also observed to contain calcitonin-sensitive AC, but the responses were of limited magnitude only and were not statistically different in Hyp and N mice. Dose-response curves showed that the decrease of the response to PTH in the proximal tubule as well as the increase of the response to calcitonin in the distal tubule were present in Hyp mice for the whole range of hormone concentrations tested. In both structures, the apparent Km for the cyclase activation by the hormone was similar in the Hyp and its paired N mouse.

Adenylyl Cyclases↗
PubMed1979

Determination of Na-K-ATPase activity in single segments of the mammalian nephron.

A micromethod for the determination of Na-K-ATPase in discrete segments of nephrons from rabbit, rat, and mouse kidneys is described. To facilitate tubule microdissection, the kidneys were perfused with collagenase after it had been verified that collagenase had no effect on ATPase activity. Individual tubule segments were dissected under stereomicroscopic observation, exposed to a hypotonic environment followed by rapid freezing, and incubated in 1 microliter assay medium. Enzyme activity was determined by direct measurement of labeled inorganic phosphate release by the hydrolysis of [gamma-32P]ATP and was expressed as a function of tubule length. This method is technically simple enough to permit simultaneous measurement of the enzyme in large numbers of tubules and sufficiently sensitive to determine its activity in each region of the nephron. Correlation of Na-K-ATPase activity in single tubules with functional measurements obtained in the corresponding segment of the nephron with the perfused tubule or micropuncture techniques should help define the role of this enzyme in tubular ion transport.

Adenosine Triphosphatases↗
PubMed1979

Na-K-ATPase activity along the rabbit, rat, and mouse nephron.

Na-K-ATPase activity along the rabbit, rat, and mouse nephron was determined with a micromethod that measures directly labeled phosphate released by the hydrolysis of [gamma-32P]ATP. Na-K-ATPase activity was highest in the rat, intermediate in the mouse, and lowest in the rabbit nephron. With the exception of rabbit cortical thick ascending limb, the enzyme profile was similar in the three species: Na-K-ATPase activity per millimeter tubule length was highest in the distal convoluted tubule and thick ascending limb of Henle's loop, intermediate in the proximal convoluted tubule, and lowest in the pars recta and collecting tubule. The enzyme was present in the thin limbs of Henle's loop, but its activity was very low and measurements were close to the sensitivity limit of the method. Both the absolute activity and the fraction of the total enzyme represented by Na-K-ATPase were severalfold higher than in kidney homogenates. Finally, the Na-K-ATPase activity measured in certain segments of the rat and rabbit nephron in this study seems sufficient to account in theory for the active component of the net sodium transport found in the corresponding region of the nephron with either in vivo or in vitro single tubule microperfusion techniques.

Adenosine Triphosphatases↗
PubMed1978

Magnesium handling in the dog kidney: a micropuncture study.

Micropuncture and clearance experiments were done on normal dogs to investigate magnesium handling by proximal and distal nephron segments. Tubular fluid electrolytes were analyzed with the electron microprobe. Tubular fluid to ultrafilterable magnesium ratio (TF/UF magnesium) was observed to rise above unity but less than the TF/P insulin ratio generated along the proximal tubule. This is in contrast to the other major cations, the ratios of which remain close to unity as water is abstracted. Tubular fluid obtained from the distal tubule contained less magnesium than the glomerular filtrate (mean TF/UF magnesium of 0.6) indicating the loop of Henle is the major nephron segment reclaiming a significant portion of the filtered load. The faction of filtered load remaining at the distal sampling site was similar to the fraction appearing in the urine (8% vs 7%) indicating very little reabsorption beyond the distal tubule in these normal states.

Animals↗