PMID- 24157978 OWN - NLM STAT- MEDLINE DCOM- 20140815 LR - 20141120 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 720 IP - 1-3 DP - 2013 Nov 15 TI - Involvement of IP3-receptor activation in endothelin-1-induced Ca(2+) influx in rat pulmonary small artery. PG - 255-63 LID - S0014-2999(13)00774-7 [pii] LID - 10.1016/j.ejphar.2013.09.076 [doi] AB - We examined the endothelin-1 (ET-1)-induced increase in the intracellular free Ca(2+) concentration ([Ca(2+)]i) in fura-2-loaded rat pulmonary small arteries. ET-1 (30 nM) elicited a long-lasting increase in [Ca(2+)]i in physiological salt solution (PSS). In subsequent experiments, arteries were pretreated with BQ-788, an ETB-specific blocker, to allow us to focus on responses mediated via the ETA receptor, the existence of which was confirmed by immunohistochemistry. In Ca(2+)-free PSS, ET-1 evoked a small transient increase in [Ca(2+)]i, indicating Ca(2+) release from the SR (sarcoplasmic reticulum). After a switch to PSS (containing 2mM CaCl2), ET-1 elicited a long-lasting increase in [Ca(2+)]i that was not inhibited by 1 muM nicardipine, an L-type Ca(2+)-channel inhibitor, suggesting involvement of a Ca(2+)-influx pathway independent of that channel. In arteries preincubated with 30 muM cyclopiazonic acid (CPA) or 2 muM thapsigargin (TG), the ET-1-induced Ca(2+)-release was greatly reduced, and the induced Ca(2+)-influx was attenuated. U-73122, a phospholipase C (PLC) inhibitor, had inhibitory effects similar to those of CPA and TG on the ET-1-induced Ca(2+)-release and Ca(2+)-influx, whereas U-73343, an inactive analogue of U-73122, had no such effects. Two putative membrane-permeable IP3-receptor blockers, 2-aminoethoxydiphenyl borate (2APB, 50 muM) and Xestospongin C (20 muM), (a) almost completely inhibited the ET-1-induced Ca(2+)-release and Ca(2+)-influx, and (b) reduced the ET-1-induced contraction. These results indicate that in rat pulmonary small arteries, ET-1 induces receptor-operated Ca(2+) influx via the ETA receptor, and that this influx interacts with InsP3-receptor activation. CI - (c) 2013 Published by Elsevier B.V. FAU - Kato, K AU - Kato K AD - Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan; Fukuoka School of Medical Sciences, Fukuoka, Japan. Electronic address: kkatou@college.fdcnet.ac.jp. FAU - Okamura, K AU - Okamura K FAU - Hatta, M AU - Hatta M FAU - Morita, H AU - Morita H FAU - Kajioka, S AU - Kajioka S FAU - Naito, S AU - Naito S FAU - Yamazaki, J AU - Yamazaki J LA - eng PT - Journal Article DEP - 20131022 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Endothelin-1) RN - 0 (Inositol 1,4,5-Trisphosphate Receptors) RN - 0 (Receptor, Endothelin A) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*metabolism MH - Endothelin-1/*metabolism MH - In Vitro Techniques MH - Inositol 1,4,5-Trisphosphate Receptors/*metabolism MH - Male MH - Pulmonary Artery/*metabolism MH - Rats MH - Rats, Wistar MH - Receptor, Endothelin A/metabolism OTO - NOTNLM OT - 2APB OT - Fura-2 OT - IP3 OT - Pulmonary artery OT - ROCC OT - Xestospongin C EDAT- 2013/10/26 06:00 MHDA- 2014/08/16 06:00 CRDT- 2013/10/26 06:00 PHST- 2013/04/03 00:00 [received] PHST- 2013/07/25 00:00 [revised] PHST- 2013/09/13 00:00 [accepted] PHST- 2013/10/26 06:00 [entrez] PHST- 2013/10/26 06:00 [pubmed] PHST- 2014/08/16 06:00 [medline] AID - S0014-2999(13)00774-7 [pii] AID - 10.1016/j.ejphar.2013.09.076 [doi] PST - ppublish SO - Eur J Pharmacol. 2013 Nov 15;720(1-3):255-63. doi: 10.1016/j.ejphar.2013.09.076. Epub 2013 Oct 22.