Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E1 and E2 (PGE) antagonize the phosphaturic effect of parathyroid hormone (PTH), but do not alter the phosphaturia evoked by adenosine 3',5'-cyclic monophosphate (cAMP) analogues. These findings support the idea that PGE interfere with activation of adenylate cyclase in the renal proximal tubule. We tested this hypothesis in the rabbit renal proximal straight tubule (PST). In the PST, adenylate cyclase was activated by PTH (Km = 10(-9) M PTH), but not by PGE2, which attenuated the activation of adenylate cyclase by PTH. The inhibition by PGE2 of PTH action was prevented by pertussis toxin, which deactivates the regulatory aggregate, Ni. In the PST, PGE2 also attenuated the activation of adenylate cyclase by cholera toxin. The inhibitory effect of PGE2 was selective; PGE2 did not inhibit activation of adenylate cyclase in glomeruli, but it inhibited the enzyme in proximal convoluted tubules (PCT) and PST. We conclude that PGE2 inhibits adenylate cyclase in rabbit proximal tubule. We propose that this action may, in part, regulate transport function in vivo.
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PMID:Prostaglandin E2 is an inhibitor of adenylate cyclase in rabbit proximal tubule. 316 52

The effect of vasoactive intestinal peptide (VIP) upon adenylate cyclase (AC) activity has been determined in defined microdissected renal tubules isolated from collagenase-treated rabbit kidneys. In the presence of 10 microM GTP, 1 microM VIP gave marked stimulations of AC over basal values in the bright portion of the distal convoluted tubule (DCTb) (10.1-fold), and in the collecting tubule isolated from the inner stripe of the outer medulla (OMCTi, 7.8-fold). Less pronounced effects of VIP were found in the medullary collecting tubule isolated from the outer stripe (2.5-fold) and in the granular portion of the distal convoluted tubule (2.0-fold). VIP stimulation of AC activity in these segments amounted to 25 to 40% of the effect elicited by other agonists (arginine vasopressin, calcitonin or parathyroid hormone) in their respective target segments. A low response to VIP was observed in the cortical thick ascending limb (1.8-fold) which represented less than 5% of the calcitonin-stimulated AC activity. In the thin descending limb VIP produced a slight and variable stimulation of AC. VIP was without effect upon AC in the convoluted and straight portions of the proximal tubule, the medullary thick ascending limb and the cortical collecting tubule. Half-maximal stimulation of AC by VIP was observed at 26 +/- 10 nM (n = 3) in OMCTi and at 19 nM (n = 2) in DCTb. Related peptides glucagon, secretin and PHI gave lower stimulations of AC compared to VIP in OMCTi. Conversely for rat OMCTi, under identical conditions, glucagon was much more effective than VIP.
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PMID:Distribution of vasoactive intestinal peptide-sensitive adenylate cyclase activity along the rabbit nephron. 317 93

These studies were designed to examine the cellular messenger that mediates the action of angiotensin II on fluid transport (Jv) in the rabbit proximal tubule. We measured the effects of angiotensin II on Jv, activation of adenylate cyclase, and the concentration of cytosolic free calcium (Cai) in the rabbit proximal tubule. In nine rabbit proximal convoluted tubules (PCT), angiotensin II, 10(-8) M and 10(-6) M, decreased Jv by 18 and 25%, P less than 0.05. In eleven rabbit proximal straight tubules (PST), 10(-8) and 10(-6) M angiotensin II decreased Jv by 20 and 23%, P less than 0.02. Angiotensin II did not affect lumen-to-bath phosphate fluxes in PCT or PST, and it did not activate adenylate cyclase in PST. In a preparation of proximal tubules (PCT and PST) loaded with aequorin, angiotensin II, 10(-8) and 10(-6) M, transiently increased Cai by 13 and 32%, P less than 0.001. We propose that Cai surges, activated by angiotensin II, are part of a cellular message that inhibits Jv in the rabbit proximal tubule.
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PMID:Intracellular messenger for action of angiotensin II on fluid transport in rabbit proximal tubule. 382 85

To evaluate the effects of parathyroid hormone and cyclic adenosine monophosphate on proximal tubular sodium and phosphate reabsorption, micropuncture studies were performed on dogs that received a highly purified preparation of parathyroid hormone (PTH), dibutyryl cyclic 3',5'-adenosine monophosphate (cyclic AMP), 5'-AMP, and saline. PTH resulted in a 30-40% inhibition of sodium and phosphate reabsorption in the proximal tubule unassociated with a rise in either total kidney or single nephron glomerular filtration rate (GFR). The bulk of the phosphate rejected proximally was excreted in the final urine while sodium excretion rose minimally despite the marked proximal inhibition, consistent with the presence of reabsorptive sites in the distal nephron for sodium but not phosphate. The infusion of dibutyryl cyclic AMP either systemically or directly into the renal artery inhibited proximal sodium and phosphate reabsorption in the absence of changes in either total kidney or single nephron GFR, resembling the effects of PTH quantitatively and qualitatively. In contrast, another adenine nucleotide, 5'-AMP, did not inhibit the reabsorption of either sodium or phosphate. These observations support the thesis that renal effects of PTH are mediated via stimulation of renal cortical adenyl cyclase. The infusion of a moderate saline load, 25 ml/kg, also produced a similar inhibition of proximal tubular fractional sodium and phosphate reabsorption with a marked phosphaturia but only minimal natriuresis. Thus, changes in sodium and phosphate reabsorption occur in parallel in the proximal tubule when sodium reabsorption is inhibited either with volume expansion or with administration of "specific" phosphaturic agents such as PTH or cyclic AMP. These data are consistent with the thesis that phosphate reabsorption is dependent upon proximal tubular sodium reabsorption wherein the phosphaturic effect of PTH might be the result of a primary inhibition of proximal tubular sodium reabsorption mediated by adenyl cyclase stimulation.
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PMID:Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog. 432 20

Isolated chick kidney proximal tubule cells have been used in a study of the mechanism by which PTH inhibits Na+-dependent Pi transport in the kidney. Treatment with PTH inhibits Pi uptake by the cells by 13% and stimulates cyclic AMP production by 77%. Forskolin, a potent activator of adenyl cyclase, brought about an 11-fold stimulation of cyclic AMP production by the cells, but in contrast to PTH, the drug had no effect on Na+-dependent Pi uptake. These results provide evidence that PTH action on phosphate transport is not mediated by cyclic AMP.
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PMID:Lack of a direct role for cyclic AMP in parathyrin action on phosphate reabsorption by the kidney. 609 34

To better understand the regulation of renal gluconeogenesis that occurs in the proximal nephron, glucose production rates from various substrates were determined in defined proximal tubule segments of the rat. Tubule segments tested were the S1 and S2 segments of superficial (SF) nephrons, the S1 segments of juxtamedullary (JM) nephrons, and the S3 segments. Glucose production (in decreasing order) was: from alpha-ketoglutarate, JM S1, SF S1, SF S2; from pyruvate, SF S2, JM S1, and SF S1; from glutamine, SF S1, JM S1; and from glutamate, SF S1 = JM S1. Little glucose was produced in the S3 segments. Glucose production from glutamate was lower than that from the other three substrates in JM S1, and glutamine was the best gluconeogenic substrate in SF S1. The effects of parathyroid hormone (PTH), a known stimulator of renal gluconeogenesis, and cAMP were examined using alpha-ketoglutarate as the substrate. Both stimulated glucose production in the S1 and S2 segments of the SF nephron. Although PTH stimulated adenylate cyclase in the S1 segments of the SF and JM nephrons, it had no effect on glucose production in the JM S1. Glucose production rose in the SF S1 and JM S1 in response to increasing concentrations of hydrogen or calcium ions, indicating that gluconeogenesis can be increased in these nephron segments. Differences may therefore be present in the cellular responses to PTH distal to cAMP formation in the nephron segments of the SF and JM nephrons. These findings show the presence of both axial and internephron heterogeneity of renal gluconeogenesis and suggest the difference in the effects of PTH on the function of SF and JM nephrons.
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PMID:Renal gluconeogenesis: axial and internephron heterogeneity and the effect of parathyroid hormone. 614 34

Cell culture, a powerful tool for the study of cell biology, offers advantages for the study of renal cell function. Epithelial cells derived from a variety of organs, including the kidney, form oriented epithelial sheets in culture that have many structural characteristics (microvilli, tight junctions) of epithelia in situ. There is evidence of transepithelial transport of salt and water by cells of two lines (MDCK and LLC-PK1) derived from mammalian kidney. LLC-PK1 cells may also manifest the glucose transport system of the proximal tubule. Cells of both lines have adenylate cyclase activity sensitive to hormones. Two lines of cells derived from toad urinary bladder form epithelia with a high transepithelial resistance and transport sodium actively from apical to basolateral surface. The rate of sodium transport in both lines is stimulated by cyclic AMP and by aldosterone. There are important differences in the characteristics of the response of the two lines to aldosterone as well as in their sensitivity to inhibition of sodium transport by amiloride. These differences may lead to new insights regarding the molecular events in the response to aldosterone and in the inhibitory action of amiloride. Cultures of kidney cells have also been used effectively to study the biosynthesis of the hormonal derivative of vitamin D and to study prostaglandin production. In addition, cell culture is ideally suited for study of the developmental biology of the kidney.
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PMID:Studies of renal cell function using cell culture techniques. 624 76

A homogeneous population of single cells from the thick ascending limb of Henle's loop (TALH) has been isolated from the rabbit kidney medulla. A total medullary cell suspension was prepared by a series of collagenase, hyaluronidase, and trypsin digestions and separated on a Ficoll gradient (2.6-30.7% wt/wt). Morphologically, the cells isolated from the TALH were homogeneous and showed polarity within their plasma membrane structure, with a few blunt microvilli on their apical surface and deep infoldings of the basal-lateral membrane. Biochemically, the TALH cells were highly enriched in calcitonin-sensitive adenylate cyclase and Na, K-ATPase. Alkaline phosphatase and arginine vasopressin-sensitive adenylate cyclase, highly concentrated in proximal tubule and collecting duct, were present only in low concentrations in the TALH cells. Additionally, furosemide, a diuretic inhibiting sodium chloride transport in the TALH in vivo, inhibited oxygen consumption of the TALH cells in a dose-dependent manner. The TALH cells were viable, as judged by morphological appearance, trypan blue exclusion, the response of oxygen consumption to 2,4-dinitrophenol, succinate and ouabain, and the cellular Na, K and ATP levels.
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PMID:Separation of renal medullary cells: isolation of cells from the thick ascending limb of Henle's loop. 625 27

Epithelial cells from a variety of species and organs form polarized epithelia in culture. When epithelia are grown on a porous surface, such as a millipore filter, transport can be studied using adaptations of standard techniques. In the few years in which cultured epithelia have been studied by transport physiologists, most work has been focused on identification and description of the differentiated transport exhibited by cultured epithelia. Epithelia formed by a continuous line of cells derived from pig kidney (LLC-PK1) exhibit sodium-coupled glucose transport similar to that of the proximal tubule and have vasopressin-sensitive adenylate cyclase that has been studied in great detail. Also of interest are epithelia formed by continuous lines of cells derived from amphibian kidney (A6) and from amphibian urinary bladder (TBM). Each line forms epithelia that have high electrical resistance and amiloride-sensitive sodium transport. Transport is stimulated by aldosterone and by cAMP or hormones that raise cell cAMP levels. In LLC-PK1 and in A6 epithelia, transport and the response to hormones can be manipulated by manipulating the culture conditions. Cultured epithelia have also been used to explore the cell biology of epithelia. Most interesting in this regard are studies of the development and maintenance of epithelial cell polarity. This approach should be especially valuable.
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PMID:Use of cultured epithelia to study transport and its regulation. 631 89

Recent studies demonstrated that prostaglandin E2 (PGE2) participates in the regulation of glomerular and distal tubular function. A functional role for PGE2 on the proximal tubule has only recently been explored. Thus, we reported that PGE2 antagonizes the phosphaturic effect of PTH in the dog, which suggests that PGE2 may influence the transport functions of the mammalian proximal tubule. The present studies were designed to examine the direct effect of parathyroid hormone (PTH) and PGE2 on the fluxes of fluid (Jv) and phosphate (Jl-b PO4) in the rabbit proximal convoluted and straight tubules (PCT and PST). The activation of adenylate cyclase by the two agents was also examined. Finally, the combined effects of PTH and PGE2 on Jv and Jl-b PO4 were also studied in the PST. In the PCT, PTH (1 microgram/ml) inhibited Jv by 31% (P less than 0.05) but did not alter Jl-b PO4. PGE2 (10(-5) M) failed to act on either Jv or Jl-b PO4. In this segment, PTH stimulated adenylate cyclase but PGE2 did not. In the PST, PTH (1 microgram/ml) inhibited Jv and Jl-b PO4 by 34 and 20%, respectively (P less than 0.01). PGE2 (10(-5) M) also inhibited Jv and Jl-b PO4, by 33 and 12%, respectively (P less than 0.02). In contrast, PGF2 alpha, a related prostanoid, failed to influence these transport parameters. In the PST, PTH activated adenylate cyclase but PGE2 failed to do so. When both PTH (1 microgram/ml) and PGE2 (10(-7) M) were present simultaneously, Jv and Jl-b PO4 were comparable to that seen during control collections.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin E2 and parathyroid hormone: comparisons of their actions on the rabbit proximal tubule. 659 16


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