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Response of Adenylate Cyclase to Parathyroid Hormone and Prostaglandins by Human Isolated Glomeruli^*

INSERM Research Unit 64, Hôpital Tenon Paris, France

Address requests for reprints to: Prof. Raymond Ardaillou, INSERM Research Unit 64, Hôpital Tenon, Paris, France.

A role for hormonal substances and other biochemical messengers in the regulation of the glomerular filtration rate has been inferred from the results of micropuncture studies in the rat and from the demonstration of hormoneresponsive adenylate cyclase activity in glomeruli isolated from the renal cortex of rats and rabbits. To investigate whether such hormonal factors may contribute to the regulation of glomerular function in humans, we studied the response of adenylate cyclase activity to the administration of human PTH-(1–34) and prostaglandins (PG) by glomeruli isolated from the renal cortex of four human kidneys. PTH and PGs (PGE₂, PGI₂, and, to a lesser extent, PGF₂) stimulated human glomerular adenylate cyclase activity. Basal adenylate cyclase activity ranged from 0.2–1.2 nmol 20 min^–1 mg^–1. For each agonist, the percent increase above basal values (at the maximum concentration tested) and the concentration of the agonist that elicited 50% of the maximum stimulation (ED₅₀) were as follows: for PTH 300–460% (10,000 mlU/ml); ED₅₀, 100–550 mlU/ml; for PGE₂, 160–380% (10 µM); ED₅₀, 0.4–1.6 µM; and for PGI₂, 180–650% (10 µM); ED₅₀, 0.09–0.46 µM. The synthetic guanylnucleotide 5'-guanylylimidodiphosphate [Gpp(NH)p] potentiated the effect of PTH and PGI₂, since the combined effects were greater than the sums of the effects of the individual agonists, and there was a significant interaction between Gpp(NH)p and PTH or PGI₂, as indicated by three-factor analysis of variance. Additivity, but not potentiation, was observed for PGE₂. The effects of PTH plus PGE₂ or PGI₂ were also additive, a finding that suggests that PTH and PGs are not linked to the same pool of adenylate cyclase. In contrast, the combination of PGE₂ and PGI₂ resulted in a significantly lower effect than the sum of their individual effects, a finding indicating that these PGs share in part a common pool of adenylate cyclase. Demonstration of PTH- and PG-dependent adenylate cyclase activity in human isolated glomeruli suggests a role for these agonists in the regulation of the glomerular filtration rate in man.

^* This work was supported by grants from INSERM and the Faculté de Medecine St. Antoine.

Received January 31, 1983.