PMID- 8760062 OWN - NLM STAT- MEDLINE DCOM- 19961203 LR - 20191210 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 271 IP - 1 Pt 1 DP - 1996 Jul TI - Ca(2+)-dependent nitric oxide release in endothelial but not R3230Ac rat mammary adenocarcinoma cells. PG - C332-7 AB - We have characterized the ability of several cell types associated with the microvasculature of solid tumors to release nitric oxide (NO.) in response to increases in cytosolic Ca2+ concentration ([Ca2+]c). EA.hy926 immortalized human umbilical vein endothelial cells (EC), rat fibroblasts (RFL), and tumorigenic cells isolated from R3230Ac rat mammary adenocarcinoma (MaC) were treated with thapsigargin (TG), an inhibitor of Ca(2+)-ATPase. NO. output was measured via a chemiluminescence detection system. Baseline NO. output was detectable only for EC. TG caused a significant increase in EC NO. output that could be blocked with NG-monomethyl-L-arginine and restored with L-arginine. TG did not stimulate NO. release from RFL or MaC cells, despite elevating [Ca2+]c in all cells. A Ca(2+)-dependent isoform of NO synthase (eNOS) was detected by immunoblot only in EC. These data indicate that EC, but not RFL or MaC, are capable of Ca(2+)-dependent NO. release and suggest that any Ca(2+)-dependent NO. release within this tumor is primarily of endothelial (and not tumorigenic cell) origin. FAU - Lindberg, R A AU - Lindberg RA AD - Department of Radiation Oncology, Duke University Medical Center, Durham 27710, USA. FAU - Dewhirst, M W AU - Dewhirst MW FAU - Buckley, B J AU - Buckley BJ FAU - Hughes, C S AU - Hughes CS FAU - Whorton, A R AU - Whorton AR LA - eng GR - CA-40355/CA/NCI NIH HHS/United States GR - HL-44740/HL/NHLBI NIH HHS/United States GR - HL-51183/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Isoenzymes) RN - 27JT06E6GR (omega-N-Methylarginine) RN - 31C4KY9ESH (Nitric Oxide) RN - 67526-95-8 (Thapsigargin) RN - 94ZLA3W45F (Arginine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - Adenocarcinoma/*metabolism/pathology MH - Animals MH - Arginine/pharmacology MH - Calcium/*physiology MH - Calcium-Transporting ATPases/antagonists & inhibitors MH - Cell Line MH - Endothelium, Vascular/*metabolism MH - Female MH - Fibroblasts/metabolism MH - Humans MH - Immunoblotting MH - Isoenzymes/metabolism MH - Mammary Neoplasms, Experimental/*metabolism/pathology MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase/antagonists & inhibitors/metabolism MH - Rats MH - Thapsigargin/pharmacology MH - omega-N-Methylarginine/pharmacology EDAT- 1996/07/01 00:00 MHDA- 1996/07/01 00:01 CRDT- 1996/07/01 00:00 PHST- 1996/07/01 00:00 [pubmed] PHST- 1996/07/01 00:01 [medline] PHST- 1996/07/01 00:00 [entrez] AID - 10.1152/ajpcell.1996.271.1.C332 [doi] PST - ppublish SO - Am J Physiol. 1996 Jul;271(1 Pt 1):C332-7. doi: 10.1152/ajpcell.1996.271.1.C332.