Parathyroid hormone stimulates juxtaglomerular cell cAMP accumulation without stimulating renin release.
Parathyroid hormone (PTH) is positively coupled to the generation of cAMP via its actions on the PTH1R and PTH2R receptors. Renin secretion from juxtaglomerular (JG) cells is stimulated by elevated intracellular cAMP, and every stimulus that increases renin secretion is thought to do so via increasing cAMP. Thus we hypothesized that PTH increases renin release from primary cultures of mouse JG cells by elevating intracellular cAMP via the PTH1R receptor. We found PTH1R, but not PTH2R, mRNA expressed in JG cells. While PTH increased JG cell cAMP content from (log(10) means ± SE) 3.27 ± 0.06 to 3.92 ± 0.12 fmol/mg protein (P < 0.001), it did not affect renin release. The PTH1R-specific agonist, parathyroid hormone-related protein (PTHrP), also increased JG cell cAMP from 3.13 ± 0.09 to 3.93 ± 0.09 fmol/mg protein (P < 0.001), again without effect on renin release. PTH2R receptor agonists had no effect on cAMP or renin release. PTHrP increased cAMP in the presence of both low and high extracellular calcium from 3.31 ± 0.17 to 3.83 ± 0.20 fmol/mg protein (P < 0.01) and from 3.29 ± 0.18 to 3.63 ± 0.22 fmol/mg protein (P < 0.05), respectively, with no effect on renin release. PTHrP increased JG cell cAMP in the presence of adenylyl cyclase-V inhibition from 2.85 ± 0.17 to 3.44 ± 0.14 fmol/mg protein (P < 0.001) without affecting renin release. As a positive control, forskolin increased JG cell cAMP from 3.39 ± 0.13 to 4.48 ± 0.07 fmol/mg protein (P < 0.01) and renin release from 2.96 ± 0.10 to 3.29 ± 0.08 ng ANG I·mg prot(-1)·h(-1) (P < 0.01). Thus PTH increases JG cell cAMP via non-calcium-sensitive adenylate cyclases without affecting renin release. These data suggest compartmentalization of cAMP signaling in JG cells.
Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI 48202, USA.
Douglas K
DK
Atchison
Pamela
P
Harding
M
M
Cecilia Ortiz-Capisano
Edward L
EL
Peterson
William H
WH
Beierwaltes
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism*; D044183:Receptor, Parathyroid Hormone, Type 2 / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*
D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; D044183:Receptor, Parathyroid Hormone, Type 2; D000242:Cyclic AMP; D012083:Renin