Renin stimulating properties of parathyroid hormone-related peptide in the isolated perfused rat kidney.
Previous studies showed that PTHrP exhibits renal vasodilating, arteriolar cAMP stimulating and receptor binding properties. The present experiments were designed to study whether PTHrP may influence renin secretion. Rat kidneys were isolated and single-pass perfused at constant flow and stabilized pressure. Exposures to PTHrP or PTH stimulated a dose-dependent renin release reaching similar Vmax. The affinity (0.1 nM) and threshold concentration (0.01 nM) for PTHrP were about 10 times lower than for PTH. Compared to 10 microM isoproterenol, the maximum renin responses to PTHrP were similar but of shorter duration. The PTHrP dose-response curve was not affected by 10 microM indomethacin. Administered simultaneously, PTHrP and PTH displayed no additive effects. PTHrP-induced renin release as well as the role of extracellular calcium were further studied in nonfiltering kidneys, which were perfused at a constant flow and stable pressure in a closed circuit. Basal renin release was inversely related with perfusate calcium and was depressed by the calcium ionophore BAY-K8644. PTHrP (100 nM) induced a 1.6-fold increase of basal renin release in normocalcic perfusate. Removing calcium abolished renin responses. PTHrP reversed the inhibiting effects of hypercalcic media or BAY-K8644 on basal renin release. The results support calcium-mediated renin stimulating properties for PTHrP, via PTH receptors, independently from baroreceptors, macula densa and prostaglandins.
Saussine
C
C
Laboratoire de Physiologie Cellulaire Rénale, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Massfelder
T
T
Parnin
F
F
Judes
C
C
Simeoni
U
U
Helwig
J J
JJ
D000818:Animals; D002118:Calcium / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010477:Perfusion; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000378:metabolism*
C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012083:Renin; D007545:Isoproterenol; D002118:Calcium; D007213:Indomethacin