Cyclic AMP increases cytoplasmic free calcium in renin-secreting cells from rat kidney.
The renin-secreting juxtaglomerular cells (JGC) in the media of the afferent arteriole at the vessel pole are the major source of circulating renin. The control of renin secretion is complex with increases in cAMP being the major stimulus and increases in intracellular free Ca2+ concentration ([Ca2+]i) being inhibitory. We measured [Ca2+]i in the afferent arteriole from mostly JGC. Manoeuvres that increase cAMP (e.g. isoproterenol) or dibutyryl-cAMP elicited an increase in [Ca2+]i which was approximately 40% of that induced by angiotensin II (3 nmol/l). The Ca2+ response occurred in 50-90% of the cases, and increasing the stimulus increased responder frequency but not response size. The response was (almost) abolished by removal of extracellular Ca2+, prevented by inhibitors of store-operated Ca2+ channels (Gd3+ and 2-aminoethoxydiphenyl-borate), but was unaffected by isradipine or protein kinase A inhibitors. It was not produced by an activator of EPACs (exchange protein activated by cAMP) and was not accompanied by changes in membrane potential. The data suggest that in rat JGC, cAMP, perhaps directly, activates store-operated Ca2+ channels to increase [Ca2+]i. One could speculate that this increase in [Ca2+]i serves to finely adjust the stimulating effect cAMP-increasing signals on the renin-angiotensin system.
Laske-Ernst
Julia
J
Department of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Tübingen, Wilhelmstr. 56, D-72074 Tübingen, Germany.
Chmielnicki
Marc
M
Quast
Ulrich
U
Russ
Ulrich
U
D000821:Animal Feed; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012965:Sodium Chloride / Q000378:metabolism
D015220:Calcium Channels; D012965:Sodium Chloride; D000242:Cyclic AMP; D012083:Renin; D002118:Calcium