Maturation of rat renal tubular response to alpha-adrenergic agonists and neuropeptide Y: a study on the regulation of Na+,K+-ATPase.
Na+,K+-ATPase in tubular cells plays a pivotal role for the regulation of renal sodium excretion. In adult rats the activity of this enzyme is inhibited by natriuretic hormones and stimulated by antinatriuretic hormones. Here we have examined the tubular response to alpha-adrenergic agonists and neuropeptide Y (NPY) in both infant and adult rats. In the adult kidney, alpha-adrenergic agonists and NPY stimulate Na+,K+-ATPase activity via Ca2+-dependent pathways. Oxymetazoline, a selective alpha-adrenergic agonist, and NPY failed to stimulate proximal tubular (PT) Na+,K+-ATPase activity in 10-d-old rats in doses of 10(-8) to 10(-5) M and 10(-8) to 10(-6) M, respectively, but when tubules were incubated simultaneously with both oxymetazoline 10(-8) M and NPY 5 x 10(-9) M, stimulation was observed in both 10- and 40-d-old rat PT. This effect was abolished by FK 506, an inhibitor of Ca2+ and calmodulin-dependent protein phosphatase 2B in both age groups. A23187, a calcium ionophore, stimulated Na+,K+-ATPase in both infant and adult PT, but 10-fold higher doses were required for the infant tubules. The effect of alpha-adrenergic agonists and NPY on free intracellular Ca2+ was studied in PT cells in primary culture. The Ca2+ response to each agent was less pronounced in infant than in adult cells. Preincubation with NPY, which increases Ca2+ influx into the cells, enhanced the response to the alpha-adrenergic agonist in both infant and adult cells. The results support the concept that the systems regulating renal tubular Na+, K+-ATPase and sodium metabolism undergo postnatal maturation.
Ohtomo
Y
Y
Karolinska Institute, Department of Woman and Child Health, St. Goran's Children's Hospital, Stockholm, Sweden.
Ono
S
S
Sahlgren
B
B
Aperia
A
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010109:Oxymetazoline / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D009478:Neuropeptide Y; D010656:Phenylephrine; D000001:Calcimycin; D010109:Oxymetazoline; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium