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Biomedical subjects

R Quigley

Publications and source records attributed to R Quigley.

7 recordsLinked to original sources
PubMed1995

Stimulation of proximal convoluted tubule phosphate transport by epidermal growth factor: signal transduction.

The present study investigated the signal-transduction pathway responsible for the epidermal growth factor (EGF) stimulation of phosphate transport (JPhos) in the rabbit proximal convoluted tubule (PCT). Genistein, 10(-4) M, bath and lumen, an inhibitor of EGF receptor tyrosine kinase activity, blocked the EGF effect on JPhos, consistent with a role for tyrosine kinase in the signal-transduction pathway. Both staurosporine (5 x 10(-8) M) and calphostin C (10(-8) M), inhibitors of protein kinase C, blocked the EGF stimulation of JPhos, indicating that protein kinase C is involved in EGF signaling. Intracellular calcium (Ca2+i) concentrations were measured in perfused tubules using fura PE3 to determine whether changes in Ca2+i were also part of the signaling pathway. After addition of 3 nM EGF, there was no change in Ca2+i, suggesting that stimulation of protein kinase C is not from phosphatidylinositol hydrolysis by phospholipase C-gamma. To determine whether phospholipase A2 (PLA2) is involved, the inhibitor mepacrine was used. Mepacrine (5 x 10(-5) M) had no direct effect on PCT transport but blocked the stimulatory effect of EGF on JPhos. PLA2 activity, assessed as free arachidonic acid release from proximal tubules in suspension, increased by 18.8% with 3 nM EGF. Thus the stimulation of JPhos by EGF is mediated via a signal-transduction pathway involving tyrosine kinase, protein kinase C, and PLA2.

Animals↗
PubMed1991

Prenatal glucocorticoids stimulate neonatal juxtamedullary proximal convoluted tubule acidification.

The rate of neonatal proximal convoluted tubule (PCT) HCO3 absorption is lower than that of adult animals. The present in vitro microperfusion study examined whether prenatal dexamethasone (60 micrograms/kg daily to the doe for 3 days before delivery) would accelerate the maturation of neonatal juxtamedullary PCT acidification. Control neonates studied within 48 h of birth had a urine pH of 7.06 +/- 0.15 and a urine HCO3 concentration of 34.3 +/- 7.0 meq/l. Animals receiving dexamethasone had a urine pH of 6.47 +/- 0.11 and a urine HCO3 concentration of 10.1 +/- 4.0 meq/l, both of which were significantly lower than control (P less than 0.01). In juxtamedullary PCTs perfused in vitro, volume absorption was 0.27 +/- 0.03 nl.mm-1.min-1 in controls and 0.39 +/- 0.02 nl.mm-1.min-1 in dexamethasone-treated animals (P less than 0.05). HCO3 absorption was stimulated in the dexamethasone group (52.6 +/- 4.6 vs. 34.1 +/- 6.3 pmol.mm-1.min-1, P less than 0.05); however, glucose transport was not significantly affected (24.8 +/- 1.3 in dexamethasone vs. 21.5 +/- 3.5 pmol.mm-1.min-1 in controls). Intracellular pH was measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyflourescin to examine whether prenatal dexamethasone stimulated the apical Na(+)-H+ antiporter and the basolateral Na(HCO3)3 symporter. Apical Na(+)-H+ antiporter proton flux was 108.5 +/- 14.2 pmol.mm-1.min-1 in the control group and 250.7 +/- 31.3 pmol.mm-1.min-1 in the dexamethasone group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Role of adenosine triphosphate (ATP) and NaK ATPase in the inhibition of proximal tubule transport with intracellular cystine loading.

Cellular cystine loading with cystine dimethyl ester inhibits volume absorption, transepithelial potential difference, glucose transport, and bicarbonate transport in proximal convoluted tubules perfused in vitro. This study examined the roles of ATP and NaK ATPase in this in vitro model of the Fanconi syndrome of cystinosis. Intracellular ATP was measured using the luciferin-luciferase assay. Intracellular ATP was reduced by 60% in proximal convoluted tubules incubated with 0.5 mM cystine dimethyl ester for 15 min at 37 degrees C (P less than 0.001). Incubation of cystine loaded tubules with 1 mM exogenous ATP increased intracellular ATP to levels not significantly different than that of controls. On the other hand, Vmax NaK ATPase activity was unchanged even though the incubation times and the concentration of cystine dimethyl ester were doubled to 30 min and 1 mM, respectively. In proximal convoluted tubules perfused in vitro, 0.5 mM cystine dimethyl ester resulted in an 89% inhibition in volume absorption (0.81 +/- 0.14 to 0.09 +/- 0.09 nl/mm.min), while there was only a 45% inhibition in volume absorption (P less than 0.01) due to cellular cystine loading in the presence of 1 mM lumen and bath ATP (0.94 +/- 0.05 to 0.52 +/- 0.11 nl/mm.min). These data demonstrate that proximal tubule cellular cystine loading decreases cellular ATP concentration, but does not directly inhibit NaK ATPase activity. The inhibition in transport and decrease in intracellular ATP due to cellular cystine loading was ameliorated by exogenous ATP. These data are consistent with cellular ATP depletion playing a major role in the inhibition of proximal tubule transport due to intracellular cystine loading.

Adenosine Triphosphate↗
PubMed1991

Effects of growth hormone and insulin-like growth factor I on rabbit proximal convoluted tubule transport.

This in vitro microperfusion study examined the effects of growth hormone and insulin-like growth factor I (IGF-I) on proximal convoluted tubule (PCT) transport. Tubules were perfused with an ultrafiltrate-like solution and bathed in a serum-like albumin solution. Neither a physiologic (5 x 10(-10) M), nor a pharmacologic (5 x 10(-8) M) dose of growth hormone had an effect on PCT phosphate or bicarbonate transport, or volume absorption. Addition of 5 x 10(-9) M and 5 x 10(-8) M IGF-I, but not 5 x 10(-10) M IGF-I, to the bathing solution resulted in an increase (12-15%) in phosphate transport, but no change in volume absorption or bicarbonate transport. Addition of IGF-I to the luminal perfusate also stimulated phosphate transport. The effect was noted at a concentration of 5 x 10(-11) M IGF-I (27% stimulation) and was maximal at a concentration of 5 x 10(-10) M IGF-I (46% stimulation). There was no effect of luminal IGF-I on volume absorption or bicarbonate transport. These data indicate that growth hormone has no direct effect on PCT transport. In the PCT, IGF-I stimulates phosphate transport specifically and acts via both basolateral and apical membranes. However, the magnitude of the maximal response to the luminal addition of IGF-I was threefold greater than that measured upon addition of the hormone to the bath, and the stimulation occurred at a 100-fold lower concentration. These data are consistent with IGF-I mediating the in vivo stimulation of phosphate transport by growth hormone.

Animals↗
PubMed1990

The attitude of parents to the use of computer-assisted interviewing in a child psychiatry service.

Before undergoing interview, parents reported that a computer-assisted interview would lack the friendly and personal approach of one conducted by a clinician but, after completing the interview, parents showed more acceptance of the procedure. Computer-assisted interviewing has the potential to play an important role in the collection of clinically relevant information from both parents and children referred to child psychiatry services.

Attitude to Computers↗
PubMed1990

Developmental changes in rabbit juxtamedullary proximal convoluted tubule bicarbonate permeability.

The bicarbonate transport rate in neonatal rabbit juxtamedullary proximal convoluted tubules (JMPCT) is lower than that in adults. The reduced rate of transport could be due to a decrease in active bicarbonate transport or an increase in the passive permeability of the tubule to bicarbonate. The present in vitro microperfusion study directly measured the bicarbonate permeability of neonatal and adult JMPCT. Bicarbonate permeability was measured at both slow and fast perfusion rates to simulate the neonatal and adult proximal tubule flow rates, respectively. At 38 degrees C in tubules perfused at 3 nL/min, bicarbonate permeability was 0.29 +/- 0.11 x 10(-5) cm/s in neonates and 1.70 +/- 0.49 x 10(-5) cm/s in adult PCT (p less than 0.05). At a perfusion rate of 10 nL/min, bicarbonate permeability was 0.11 +/- 0.27 x 10(-5) cm/s in neonatal PCT and 2.31 +/- 0.15 x 10(-5) cm/s in adult PCT (p less than 0.05). These results demonstrate that bicarbonate permeability in neonatal JMPCT is significantly lower than that in adult JMPCT. Thus, the lower rate of bicarbonate transport in neonatal PCT is entirely due to a lower rate of active bicarbonate transport.

Animals↗