We have previously investigated, in studies of rat distal colonic mucosa, the effect of ATP added to the basolateral side on ion transport and [Ca2+]i. It was demonstrated that ATP acts via a P2Y1 receptor to increase [Ca2+]i and NaCl secretion. In the present study we investigated the effect of luminally added nucleotides (ATP, UTP) on transepithelial voltage (Vte) and resistance (Rte) in Ussing chamber experiments on rat distal colonic mucosa. Both nucleotides induced a rapid and transient (within 30 s) change of Vte to lumen-positive values (resting Vte: -2+/-1 mV; peak Vte after 100 micromol/l ATP: +2.4+/-1.1 mV) and a decrease of Rte from 89. 9+/-10.3 to 83.8+/-9.1 Omegacm2 (n=10). Similar values were obtained with luminal UTP (n=15). The estimated EC50 values for both nucleotides were approximately 6 micromol/l. The ATP-induced Vte effect was nearly completely sensitive to Ba2+. Addition of the K+ channel blocker Ba2+ (1 mmol/l) to the luminal solution reversibly inhibited 77+/-4% (n=5) of the ATP-induced Vte effect. Experiments to identify the respective P2 receptor subtype revealed the following rank order of potency at 500 micromol/l agonist: UTP>/=ATP>>2-methylthio-ATP=ADP>>adenosine> AMP>beta, gamma-methylene-ATP (n=5). This closely resembles the published rank order for the P2Y2 receptor. Using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique P2Y2 receptor-specific mRNA was detected in total RNA extracted from isolated crypts. In summary these data indicate that luminal ATP and UTP act via a P2Y2 receptor in the luminal membrane of colonic mucosa to elicit a transient K+ secretion.

Normal serum creatinine (Scr) and creatinine clearance (Ccr) values during the first 10 days of life were obtained in 63 very premature (28-32 weeks of gestation), premature (33-37 weeks) and term infants (38-42 weeks). Scr fell, and Ccr rose less markedly in the very premature infants. Scr was 80 mumol/l on the 1st day of life both in very premature and premature infants, and 77 mumol/l in full-term neonates. After 10 days, Scr was 73, 53 and 35 mumol/l respectively. There was an exponential correlation between Ccr and gestational age, indicating rapid maturation of glomerular function.

The incidence of hypertension was sought in 102 children who had undergone renal transplantation. Fifty five were being treated with cyclosporin and 47 with azathioprine, and they were foliowed up for a maximum of five years. After one year 35 of those receiving cyclosporin (64%) and 34 of those receiving azathioprine (72%) were hypertensive; after five years the figures were 5/6 (83%) and 25/35 (71%), respectively. Recipients of grafts from living related donors had a lower incidence of hypertension than recipients of cadaveric grafts. The incidence of hypertension was higher in patients with acquired original kidney disease than in children with congenital or familial diseases. In both groups creatinine clearance and the frequency of acute rejection episodes did not differ between normotensive and hypertensive patients. When the lowest concentrations of cyclosporin in whole blood were more than 400 ng/ml the incidence of hypertension one year after transplantation was higher. The incidence of hypertension after renal transplantation in children is higher than that reported in adults. Acquired original disease, transplantation of cadaveric grafts, and nephrotoxicity of cyclosporin are ail contributory factors.Hypertension after renal transplantation poses a considerable therapeutic problem to the nephrologist. Transient hypertension immediately after the transplant is found in almost all cases.' The main concern, however, is persistent hypertension with cardiovascular and cerebrovascular complications, and increased mortality and morbidity.2 3 The aim of the present study was to investigate the incidence and possible causes of hypertension after transplantation in children and adolescents, and to compare two different treatment regimenscyclosporin and azathioprine. be evaluated in the cyclosporin study group. Ninety seven recipients were treated with azathioprine alone, and 62 grafts functioned for more than a year. Thirty five organs were lost because of irreversible rejection, thrombosis and recurrence of oxalosis, and 15 patients were lost to follow up. Thus 47 patients receiving conventional immunosuppression with azathioprine and high dose prednisolone could be evaluated.Our treatment regimens for azathioprine and cyclosporin have been described elsewhere.4 5 The mean (SD) age at the time of renal transplantation was 11-7 (3-4) years in the azathioprine group and 12-4 (4-0) years in the cyclosporin group. Histories were obtained from the case notes, and included information about hypertension before transplantation, and previous treatment with steroids. Hypertension was defined as persistent blood pressure readings above the 95th percentile (according to Horan et a16) that required antihypertensive treatment. Severe hypertension was defined as blood pressure readings necessitating treatment with three or more antihypertensive drugs in maximum or near maximum dosage.Antihypertensive regimens varied, and the following drugs were used in a 'stepped care' approach: propranolol (dose range: 0-85-8 mg/kg...

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First, CAA inhibits the Na+/Ca2+-exchanger. Second, this effect is dependent on PKA. Third, CAA induces necrotic rather than apoptotic cell death. Finally, disturbed Ca(2+) homeostasis via Na(+)/Ca(2+) exchange contributes to the nephrotoxic action of CAA in RPTEC.