PMID- 10556932 OWN - NLM STAT- MEDLINE DCOM- 20000124 LR - 20240315 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 128 IP - 5 DP - 1999 Nov TI - Effects of cyclopiazonic acid on contraction and intracellular Ca2+ in oesophageal striated muscle of normotensive and spontaneously hypertensive rats. PG - 961-8 AB - 1. The effects of cyclopiazonic acid (CPA), a selective inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, on twitch contraction and on the resting state of tension and intracellular Ca2+ level ([Ca2+]i) of the oesophageal striated muscle of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) were compared. 2. CPA (10 micronM) augmented the twitch contraction of oesophageal striated muscle preparations from both SHRSP and WKY, reducing the rate of relaxation (-dT/dt), and thus resulting in the prolongation of the time to 80% relaxation. The effect was significantly smaller in the SHRSP preparations. 3. In the resting state, CPA caused a sustained elevation of [Ca2+]i. The elevation was greater in the WKY preparations. Tension development accompanied by the elevation was observed in WKY preparations, but not in SHRSP preparations. 4. The sustained elevation of [Ca2+]i induced by CPA was eliminated by the removal of extracellular Ca2+. Both the elevated [Ca2+]i and tension in the preparations from WKY were reduced by flufenamic acid (100 micronM), mefenamic acid (100 micronM), lanthanum (La3+, 100 micronM), gadolinium (Gd3+, 100 micronM) and SK&F 96365 (100 micronM) but not by verapamil (10 micronM). 5. Thapsigargin (3 micronM), another SR Ca2+-ATPase inhibitor, produced similar effects on basal tension to those of CPA, although it reduced the amplitude of twitch contraction. 6. These results suggest that in the rat oesophageal striated muscle, (1) CPA extends the sequestrating time of Ca2+ into the SR, (2) CPA induces a Ca2+ influx mediated through verapamil-insensitive pathways, possibly nonselective cation channels, and (3) the mechanism of [Ca2+](i) modulation due to CPA-sensitive SR Ca2+-ATPase is deteriorated in the oesophageal striated muscle from SHRSP as compared with WKY preparations. FAU - Sekiguchi, F AU - Sekiguchi F AD - Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. FAU - Shimamura, K AU - Shimamura K FAU - Kawata, K AU - Kawata K FAU - Nakazawa, Y AU - Nakazawa Y FAU - Saitoh, R AU - Saitoh R FAU - Yanagitani, Y AU - Yanagitani Y FAU - Sunano, S AU - Sunano S LA - eng PT - Journal Article PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 0 (Ion Channels) RN - 67526-95-8 (Thapsigargin) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) RN - X9TLY4580Z (cyclopiazonic acid) SB - IM MH - Animals MH - Blood Pressure/drug effects MH - Body Weight/drug effects MH - Calcium/*metabolism MH - Calcium-Transporting ATPases/*antagonists & inhibitors MH - Enzyme Inhibitors/*pharmacology MH - Esophagus/drug effects/*metabolism MH - Hypertension/genetics/*metabolism MH - In Vitro Techniques MH - Indoles/*pharmacology MH - Ion Channels/drug effects MH - Male MH - Muscle Contraction/drug effects MH - Muscle, Smooth/*drug effects/metabolism MH - Rats MH - Rats, Inbred SHR MH - Rats, Inbred WKY MH - Sarcoplasmic Reticulum/drug effects/enzymology MH - Thapsigargin/pharmacology PMC - PMC1571716 EDAT- 1999/11/11 00:00 MHDA- 1999/11/11 00:01 PMCR- 2000/11/01 CRDT- 1999/11/11 00:00 PHST- 1999/11/11 00:00 [pubmed] PHST- 1999/11/11 00:01 [medline] PHST- 1999/11/11 00:00 [entrez] PHST- 2000/11/01 00:00 [pmc-release] AID - 0702867 [pii] AID - 10.1038/sj.bjp.0702867 [doi] PST - ppublish SO - Br J Pharmacol. 1999 Nov;128(5):961-8. doi: 10.1038/sj.bjp.0702867.