Modulation of calcium movements by urocortin II in endothelial cells.
BACKGROUND
In endothelial cells urocortin II has recently been found to activate nitric oxide synthase through cAMP-dependent and Ca(2+)-related pathway.


OBJECTIVE
The present study was therefore planned to determine the mechanisms of urocortin II effect on Ca(2+) movements.


METHODS
In Fura-2 loaded porcine aortic endothelial cells (PAE), the effects of urocortin II on [Ca(2+)]c were analyzed and compared with those of various K(+) channels agonists/antagonists.


RESULTS
In Fura-2 loaded PAE, urocortin II promoted a transient increase of [Ca(2+)]c mainly originating from an intracellular pool sensitive to thapsigargin and slightly from the extracellular space. In addition, urocortin II caused the hyperpolarization of plasma membrane through the opening of K(+) channels, which contributed to the increased [Ca(2+)]c. These effects were abolished by the corticotropin releasing factor receptors (CRFR2) blocker, the adenylyl cyclase and Ca(2+)-calmodulin-kinase (CaMKII) inhibitors and by blockers of K(+) channels. In addition, in PAE cultured in Na(+)-free medium or loaded with the plasma-membrane Ca(2+) pump inhibitor the urocortin II-evoked Ca(2+) transient was slower.


CONCLUSIONS
The results obtained show that urocortin II affects intracellular Ca(2+) homeostasis in PAE by both promoting a discharge of intracellular pool and by interfering with the operation of store-dependent channels through CRFR2-cAMP-CaMKII related signalling and K(+) channels opening.
Grossini
Elena
E
Laboratorio di Fisiologia, Dipartimento di Medicina Clinica e Sperimentale, Facoltà di Medicina e Chirurgia, I-28100 Novara, Italy. grossini@med.unipmn.it
Caimmi
Philippe Primo
PP
Molinari
Claudio
C
Mary
David A S G
DA
Uberti
Francesca
F
Vacca
Giovanni
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D008564:Membrane Potentials; D015221:Potassium Channels / Q000378:metabolism; D013552:Swine; D019284:Thapsigargin / Q000494:pharmacology; D054832:Urocortins / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D054832:Urocortins; D019284:Thapsigargin; D002118:Calcium; D016257:Fura-2