Coordination of calcium signalling by endothelial-derived nitric oxide in the intact liver.
Calcium ions (Ca2+) and nitric oxide (NO) are key signalling molecules that are implicated in the regulation of numerous cellular processes. Here we show that, in the intact liver, stimulation of endothelial cells by bradykinin coordinates the propagation of vasopressin-dependent intercellular Ca2+ waves across hepatic plates, and markedly increases the frequency of Ca2+ oscillations in individual hepatocytes. Modulation of Ca2+ oscillations by bradykinin is lost following isolation of hepatocytes, but restored in co-cultures of hepatocytes and endothelial cells. The sensitizing effects of bradykinin are mimicked by NO donors and abrogated by NO inhibitors. Thus, crosstalk between NO and Ca2+ signalling pathways through the microvasculature is probably an important mechanism for the coordination of liver function and may have a function in other organs.
Patel
S
S
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
Robb-Gaspers
L D
LD
Stellato
K A
KA
Shon
M
M
Thomas
A P
AP
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000494:pharmacology
D001565:Benzoates; D007093:Imidazoles; D020030:Nitric Oxide Donors; D014667:Vasopressins; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester