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Biomedical subjects

W H Dantzler

Publications and source records attributed to W H Dantzler.

At least 91 records · Page 5Linked to original sources
PubMed1984

Effects of low [Ca2+] and La3+ on PAH transport by isolated perfused renal tubules.

Effects of low medium calcium concentration and of lanthanum on p-aminohippurate (PAH) transport by isolated perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Nominal removal of calcium from bath produced rapid, irreversible disruption of cells and depression of net PAH secretion (JPAH). However, nominal removal of calcium from lumen with calcium in bath reversibly depressed JPAH and apparent PAH permeability of luminal membrane without altering net fluid absorption (Jv) or intracellular PAH concentration [( PAH]cell). In the presence of calcium (1.8 mM), lanthanum (2 mM) in perfusate alone, in bath alone, or in both perfusate and bath reversibly depressed JPAH, apparent PAH permeabilities of luminal and peritubular membranes, and initial rate of PAH transport into cells without altering [PAH]cell or Jv. Variations in calcium concentration had little effect on depression of JPAH in sodium-free bath. These data suggest that calcium entry into cells, but possibly not cytosolic calcium concentration alone, is important for PAH transport from bath into cells and from cells into lumen and for normal passive permeability of peritubular membrane to PAH and that increased cytosolic calcium concentration is not primarily responsible for depression of JPAH in sodium-free medium.

Aminohippuric Acids↗
PubMed1984

Verapamil and quinidine effects on PAH transport by isolated perfused renal tubules.

The effects of verapamil and quinidine on p-aminohippurate (PAH) transport by isolated perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Addition of 5 X 10(-5) M verapamil or 1 X 10(-4) M quinidine to the bath reversibly depressed net PAH secretion (JnetPAH), apparent permeabilities of luminal (PL) and peritubular membranes (Pp) to PAH, and initial rate of PAH transport into cells at the peritubular membrane without affecting net fluid absorption (Jv), but simultaneously produced a threefold increase in cellular PAH concentration ( [PAH]cell). Addition of 5 X 10(-5) M verapamil to the perfusate reversibly depressed JnetPAH and PL without affecting [PAH]cell or Jv. Tetraethylammonium (1 X 10(-3) M) did not alter the effects of verapamil on PAH transport. The data indicate that verapamil and quinidine in the bath inhibit JnetPAH by inhibiting uptake into cells across peritubular membrane and efflux from cells across luminal and peritubular membranes and possibly by producing intracellular binding, verapamil in the perfusate inhibits JnetPAH by inhibiting efflux from cells across the luminal membrane and probably uptake into cells across the peritubular membrane, and the verapamil effects on JnetPAH do not depend on its entry into cells. The effects of verapamil may result primarily from inhibition of calcium entry into cells, but both verapamil and quinidine may have effects on PAH transport independent of effects on calcium.

Aminohippuric Acids↗
PubMed1984

Tetraethylammonium transport by isolated perfused snake renal tubules.

Tetraethylammonium (TEA) transport was studied in isolated perfused snake (Thamnophis spp.) proximal renal tubules. Unidirectional lumen-to-bath (J1----bTEA) and bath-to-lumen (J1----bTEA) fluxes exhibited saturation kinetics, but Jb----1TEA also exhibited an apparent diffusive component and J1----bTEA did not. Jb----1TEA exceeded J1----bTEA at all concentrations studied, resulting in net TEA secretion. Transport into cells across both luminal and peritubular membranes was apparently against an electro-chemical gradient and was inhibited by cyanide. Km for J1----bTEA (5.9 microM) was about one-third Km for Jb----1TEA (19.9 microM), indicating greater affinity of the luminal transporter for TEA; but Vmax for Jb----1TEA (153 fmol X min-1 X mm-1) was about six times Vmax for J1----bTEA (27 fmol X min-1 X mm-1), indicating a greater capacity of the peritubular transporter for TEA, which could account for net TEA secretion. Jb----1TEA was inhibited by N-methylnicotinamide (NMN) in the bath, but J1----bTEA was inhibited initially and then apparently transstimulated by NMN in the lumen, indicating possible countertransport. J1----bTEA, but not Jb----1TEA, was significantly reduced by replacement of sodium with sucrose, indicating possible sodium dependency of the luminal transporter. All data indicate active (either primary or secondary) TEA transport at both luminal and peritubular membranes but net transepithelial transport in the bath-to-lumen direction.

Animals↗
PubMed1983

Micropuncture study of urate transport by superficial nephrons in avian (Sturnus vulgaris) kidney.

Tubule fluid samples from proximal tubules of superficial, reptilian-type nephrons of the European starling (Sturnus vulgaris) were obtained by micropuncture and, along with plasma samples, were analyzed for urate by high performance liquid chromatography with electrochemical detection, as well as for the elements sodium, chloride, calcium, magnesium, phosphorus and potassium by electron microprobe analysis. All proximal tubules sampled showed net secretion of urate, but the magnitude of transport was highly variable. Mean fractional delivery of urate to the point of micropuncture was 4.04 +/- 0.37 (mean +/- SE, n = 40 tubules). Fractional delivery of urate could not be correlated with fractional delivery of any of the measured elements or with relative fluid absorption. Samples collected from surface segments of cortical collecting ducts suggest that, although much net secretion of urate occurs early within the proximal tubule of superficial nephrons, some additional secretion may occur in more distal segments. Fractional excretion of urate at the level of the cloaca averaged 4.72 +/- 0.97 for nine birds, confirming the result of overall net secretion of urate previously reported for other avian species. These results clearly demonstrate the presence of significant secretory transport of urate in the proximal tubule of superficial reptilian-type nephrons, but do not rule out the possibility of additional secretory or reabsorptive fluxes at other sites.

Animals↗
PubMed1983

Effects of sulfhydryl reagent, p-chloromercuribenzoate, on p-aminohippurate transport by isolated, perfused snake renal tubules.

Effects of mercaptide-forming sulfhydryl reagent, p-chloromercuribenzoate (PCMB), on transport of p-aminohippurate (PAH) by isolated, perfused snake (Thamnophis species) renal tubules were studied. PCMB (10(-7) mol/l) in bathing medium irreversibly inhibited net transepithelial transport of PAH (JPAH) without affecting net fluid absorption (Jv). PCMB (10(-8) mol/l) in perfusate irreversibly inhibited JPAH without affecting Jv and markedly reduced the apparent permeability of the luminal membrane to PAH. These data suggest that sulfhydryl groups may be involved in the PAH transport steps at both the peritubular and luminal membranes.

Aminohippuric Acids↗
PubMed1982

Micropuncture of superficial nephrons in avian (Sturnus vulgaris) kidney.

Single nephron glomerular filtration rate (SNGFR), fluid absorption, and tubule transport of sodium, chloride, calcium, magnesium, potassium, and phosphate were evaluated under control (2.5% mannitol infusion) conditions by micropuncture of superficial, reptilian-type nephrons of European starlings (Sturnus vulgaris). SNGFR averaged 0.36 nl . min-1 . Sodium, chloride, and water were transported at equivalent rates with about 24% of the filtered load absorbed up to the point of micropuncture. Calcium was absorbed continuously along these tubules in excess of sodium and fluid, whereas magnesium appeared to undergo net secretion early and net absorption late in the tubules. Potassium transport varied considerably, with all tubules from a single bird generally showing either net potassium absorption or no net transport. In the latter group, data for a few tubules suggested net potassium secretion. For phosphate, individual tubules from a single bird were capable of either net absorption or net secretion. Mean fractional delivery of phosphate for all tubules was 1.62, but secretion rates apparently can exceed filtration rates for phosphate by as much as 6 times.

Animals↗
PubMed1982

Reptilian glomerular and tubular functions and their control.

Controls for glomerular filtration (GFR) and tubular transport of solutes and water are interrelated. GFR changes with hydration, apparently as a result of changes in the number of filtering nephrons under the control of antidiuretic hormone. The resulting alterations in volume flow rate through the collecting ducts may be as important as changes in epithelial permeability in determining urine osmolarity. Tubular transport of sodium and potassium may be controlled in part by antidiuretic hormone and aldosterone but considerable variation occurs among species, and intrinsic regulation of distal tubular sodium absorption in response to the delivered load of sodium may also occur. Net tubular secretion of phosphate, under control of parathyroid hormone, occurs in some species, but no hormonal control of tubular calcium transport has been demonstrated. Net tubular urate secretion that is influenced by potassium occurs in uricotelic reptiles. Complexing of inorganic cations, especially sodium and potassium, with urate precipitates in tubular urine permits excretion of cations without their contributing to urine osmolarity. This process also may keep the distal tubule sodium concentration low enough to permit maximum dilution but may require absorption of filtered water without sodium. Such an absorptive process may exist in reptilian proximal tubules.

Aldosterone↗
PubMed1981

Effects of chloride substitutes on PAH transport by isolated perfused renal tubules.

Effects of substituting isethionate, methyl sulfate, or thiocyanate for chloride on p-aminohippurate (PAH) transport by isolated perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. In the perfusate, isethionate or methyl sulfate substitution irreversibly depressed net PAH secretion and the apparent PAH permeability of the luminal membrane by about 60-80%, whereas thiocyanate substitution had no effect. In the bathing medium, isethionate substitution reversibly stimulated net PAH secretion by about 35% without changing the apparent permeability of the peritubular membrane to PAH (Pp); thiocyanate substitution reversibly inhibited net PAH secretion by about 45% without affecting Pp; and methyl sulfate substitution had no effect. With simultaneous substitutions in perfusate and bath, isethionate depressed net PAH secretion irreversibly, whereas thiocyanate had no effect. Effects on PAH transport were not simply the result of changes in transepithelial potential or of the changes in net transepithelial fluid movement. These data strengthen the concept that net PAH secretion involves different mediated steps at the peritubular and luminal membranes. Since these tubules are highly permeable to thiocyanate and poorly permeable to isethionate and methyl sulfate, the data suggest that the mediated step from cells to lumen does not require chloride in the lumen but does require a highly permeant anion.

Aminohippuric Acids↗
PubMed1980

Comparative nephron function in reptiles, birds, and mammals.

Volume and osmolarity of urine produced by kidneys of reptiles, birds, and mammals depend on anatomic relationships among nephrons, epithelial permeability to water controlled by antidiuretic hormone, and, for reptiles and birds, probably on volume flow rate through collecting ducts and excretion of uric acid. Urine volume and volume flow rate through collecting ducts in reptiles and birds depend on number of filtering nephrons controlled by antidiuretic hormone. Mammalian nephrons do not filter intermittently but control of nephron filtration rates in all three vertebrate classes may have important similarities and differences. Uric acid excretion by birds and many reptiles permits excretion of inorganic cations in excess of amounts permitted by osmolarity of urine. This process may require tubular absorption of water without sodium. Such absorption, which has been found in reptilian proximal tubules, may be very important for osmoregulation in all birds and uricotelic reptiles and may provide insight into the mechanism of fluid absorption in mammals. Urea excretion in mammals may be important for enhancing concentrating ability. Much more must be learned about these processes, but similarities and differences among them in the three vertebrate classes may help illuminate details of each.

Animals↗
PubMed1980

Bath and lumen effects of SITS on PAH transport by isolated perfused renal tubules.

Effects of 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene (SITS) in bath or lumen on p-aminohippurate (PAH) transport by isolated perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Addition of SITS to the bath in concentrations as low as 10(-10) M irreversibly depressed net PAH secretion. Addition of 10(-4) M SITS in the bath depressed net PAH secretion by about 60% without affecting apparent permeability of luminal membrane to PAH (PL) or net fluid absorption. Cellular PAH concentration was reduced by about 70% at this time but was still greater than that in the bath. Apparent permeability of peritubular membrane, determined from PAH efflux from tubules with oil-filled lumens, was unchanged even with 10(-3) M SITS in bath. These data indicate that SITS in the bath inhibits PAH transport from bath into cells without enhancing passive efflux from cells to bath. Addition of 10(-4) M SITS to the lumen alone depressed net PAH secretion and PL by about 60%, but this depression was reversed when SITS was removed from the lumen. These data suggest that PAH moves from cells to lumen by a mediated process distinctly different from that fro transport into cells from bath.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1980

Significance of comparative studies for renal physiology.

Comparative studies contribute significantly to determining principles of renal physiology. Examples of comparative relationships important for past, current, or future studies are discussed. Structural simplicity of the avian glomerulus may permit detailed analysis of filtration pressure profiles. Alterations in nephron function, redistribution of filtration among nephron populations, and control by antidiuretic hormone and other factors are readily demonstrable in nonmammalian vertebrates. Studies of the distal tubule-glomerular feedback mechanism may be particularly revealing in nephrons of nonmammalian vertebrates, many of which lack a macula densa. The influence of volume flow rate in collecting ducts on the concentrating mechanism can be analyzed readily in avian kidneys in which glomerular intermittency influences such flow. The structure of Henle's loops may be related to the importance of sodium, chloride, and urea in avian and mammalian concentrating mechanisms. Perfusion of isolated reptilian renal tubules to study urate transport has also raised questions about fluid absorption and may permit more detailed analysis of some other transport systems than perfusion of mammalian tubules. Simplicity of some nonmammalian systems and exaggerated functions in these systems should continue to make them useful for revealing basic principles of renal function.

Alligators and Crocodiles↗
PubMed1980

Electrical characteristics of snake distal tubules: studies of I-V relationships.

Distal tubules of Thamnophis spp. were perfused in vitro with Ringer solution containing either 16 or 150 mM Na and bathed with 150 mM Na Ringer. Current-voltage relationships were obtained by injecting pulses of constant current, Io, into the tubule lumen and recording changes in voltage, delta Vo, at the proximal end of the perfused tubule segment. The Io-Vo plots showed a distinct break at a voltage E1 (approximately 85 mV) that was greater than the open-circuit voltage, VToc, and similar to values of ENa, the transepithelial driving force for Na transport estimated by other methods. The resistance of the shunt pathway, Rs, was estimated from the values of the transepithelial resistance after luminal addition of 10(-5) M amiloride, which caused a rapid fall of the VToc to 0 mV with concurrent increases of the transepithelial resistance. These estimates of Rs were the same as the values of E1/I1 obtained from the Io-Vo plots. The VToc, RT, and Rs were independent of the bath [Na] and were not influenced by the addition of amiloride to the bath. As in frog skin and toad urinary bladder, the ENa and Rs of the snake distal tubule can be estimated from studies of their Io-Vo plots, and the E1 appears to be independent of the transepithelial chemical potential for Na.

Amiloride↗
PubMed1980

Luminal Na concentration and the electrical properties of the snake distal tubule.

In previous studies of isolated perfused distal tubules of Thamnophis spp., elevation of luminal [Na] from 16 to 150 mM resulted in a transient hyperpolarization of the open-circuit voltage, VToc. To characterize further this response, studies were done to examine the concurrent changes of the transepithelial resistance, RT. After elevation of luminal [Na] from 16 to 150 mM. the VToc increased sharply from a mean of 38.5 to 61.2 mV and the RT decreased from a mean of 22.3 to 15.8 k omega x cm. Thereafter, the VToc declined slowly below control values, and the RT increased well above control values. The short-circuit current calculated as VToc/RT changed in parallel with the VToc, increasing at first (from 1.8 to 4.1 microA/cm) and then falling to about 0.2 microA/cm. Luminal addition of 10(-5) M amiloride caused th VToc leads to 0 and the RT to increase during control and all phases of the transient. On the assumption that RT during amiloride perfusion is the same as the shunt resistance, Rs, the values of the transepithelial driving force, ENa, and its series resistance, RNa, were calculated. An analysis of the data in this way indicated that the principal changes in the epithelium could be attributed to alterations of the RNa and not the ENa or Rs.

Amiloride↗
PubMed1979

Effects of inhibitors in lumen on PAH and urate transport by isolated renal tubules.

Effects of the presence of unlabeled p-aminohippurate (PAH) or urate, probenecid, and phenol red in the lumen on labeled PAH or urate transport by isolated, perfused snake (Thamnophis spp.) proximal renal tubules were studied. Net secretion of labeled urate and luminal membrane permeability to urate were unaffected by the presence of unlabeled urate (up to 0.1 mM) or probenecid (up to 1.0 mM) in lumen only. The data are compatible with movement of urate from cells to lumen during urate secretion by a simple passive process. Net secretion of labeled PAH was rapidly and reversibly depressed to about 25-35% of control when unlabeled PAH (0.05 mM), phenol red (0.05 mM), or probenecid (0.1 mM) was added to the lumen only. During maximum depression of PAH transport, luminal membrane permeability to PAH was reduced by 60-70%. The data suggest that movement of PAH from cells to lumen down an electrochemical gradient during PAH secretion occurs by a readily inhibited, mediated process.

Animals↗
PubMed1978

Fluid absorption with and without sodium in isolated perfused snake proximal tubules.

Net fluid absorption (JV) was studied in isolated, perfused snake (Thamnophis spp.) proximal renal tubules. With standard (150 mmol/liter Na+) bicarbonate-buffered Ringer in perfusate and standard Ringer plus dextran (4 g/100 ml) in bath, JV was about 0.9 nl min-1 mm-1. Removing dextran from bath reduced JV by about 20 percent. When sodium in perfusate was replaced with choline JV approached zero. However, when sodium in bath as well as perfusate was replaced with choline, JV returned to control level. Results were the same when sodium was replaced with tetramethyl-ammonium, sodium chloride was replaced with sucrose or lactose, or chloride was replaced with methyl sulfate. In contrast, replacing sodium in perfusate or in both perfusate and bath with lithium did not reduce JV. Fluid absorption was always isosmotic. Replacing bicarbonate with phosphate or Tris in sodium-containing media had no effect on JV, but the presence of buffer in sodium-free or low-chloride media may have been important for JV. Reducing temperature 10 degrees C reduced JV by about 35 percent with either sodium chloride or sucrose in both perfusate and bath. The results indicate that isosmotic fluid absorption can occur when lithium is substituted for sodium or when some other substitution is made for sodium, chloride, or both in perfusate and bath simultaneously.

Animals↗
PubMed1978

Generation of transepithelial potentials by isolated perfused reptilian distal tubules.

Transepithelial potentials were measured in the most distal segments of garter snake (Thamnophis spp.) distal tubles perfused in vitro. The segments generated high lumen-negative potentials when sodium was in the lumen. The size of the potentials was a saturable function of luminal sodium concentrations between 0 and 32 mM. The potentials were stable with time only when sodium concentrations in the lumen were less than 30 mM. Perfusion with high sodium concentrations resulted in transient potentials. Stable potentials changed markedly when the lumen sodium concentration or the bath potassium concentration was altered suddenly, but they were independent of lumen potassium concentrations and bath sodium concentrations. Amiloride stimulated or inhibited the potentials, ouabain partially depressed them, and ethacrynic acid and cyanide inhibited them slowly and often irreversibly. We conclude that distal transepithelial potentials reflect sodium transport from lumen to bath across a tight asymmetric epithelium which differs from other sodium-transporting epithelia in that stable transepithelial potentials are maintained only with luminal sodium concentrations less than 30 mM.

Amiloride↗