Abstract:
:1. The effects of ryanodine on changes in cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension induced by maximum concentrations of phenylephrine (Phe; 1 microM), prostaglandin F2 alpha (PGF2 alpha, 10 microM), caffeine (Caf, 30 mM) and isoprenaline (Iso, 1 microM) were examined in rat aortic strips using fura-2. 2. In normal media, Phe and PGF2 alpha produced a phasic contraction, followed by a tonic one. Caf elicited only a transient contraction. When the preparation was treated with 10 microM ryanodine, an increase in [Ca2+]i was induced accompanied by a nicardipine (1 microM)-resistant contraction which was [Ca2+]o-dependent. 3. In Ca2(+)-free solution, the three stimulants elicited transient increases in [Ca2+]i. Transient contractions to Phe and Caf were accompanied by changes in [Ca2+]i. The transient increase in [Ca2+]i induced by PGF2 alpha was not accompanied by a corresponding contraction. 4. Sustained contractions were induced by Phe and PGF2 alpha in the absence of external Ca2+, while the increase in [Ca2+]i was reduced. A larger maximum contraction was induced by PGF alpha than by Phe. 5. Ryanodine abolished both the Caf- and Phe-induced [Ca2+]i transient increases and the corresponding contractions, but had no substantial effect on the PGF2 alpha-induced [Ca2+]i transient increase. Ryanodine had no influence on the sustained contractions induced by Phe and PGF2 alpha. 6. Iso relaxed both sustained contractions almost completely, without any detectable change in [Ca2+]i. Treatment of the preparation with ryanodine had no effect on the concentration-response curves for Iso in relaxing the 0.1 microM Phe- or 40 mM K(+)-induced precontraction. 7. It is suggested that Phe and Caf mobilize Ca2 + from a ryanodine-sensitive Ca2 + store and that PGF2 alpha. releases Ca2+ from a ryanodine-insensitive Ca2+ store. The former contributes to the transient contraction through a Ca2'-dependent process, while the latter seems not to be directly associated with the contraction. The sustained contraction under Ca2+-free conditions might involve a Ca2 '-independent process or a change in the sensitivity of the contractile filaments to Ca2 + 8. In addition to lowering cytoplasmic Ca2+ concentration, it is suggested that Iso counteracts the apparently Ca2 +-independent process. The ryanodine-sensitive Ca2+ store plays no substantial role in active relaxation by Iso, although it does play a major role in the maintenance of cytoplasmic Ca2+ in a quiescent muscle.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Hisayama T,Takayanagi I,Okamoto Ydoi
10.1111/j.1476-5381.1990.tb14075.xsubject
Has Abstractpub_date
1990-08-01 00:00:00pages
677-84issue
4eissn
0007-1188issn
1476-5381journal_volume
100pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects o...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1994.tb14059.x
更新日期:1994-01-01 00:00:00
abstract::We investigated the ability of N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide (AC-5216), a novel mitochondrial benzodiazepine receptor (MBR) ligand, to produce anti-anxiety and antidepressant-like effects in various animal models. AC-5216 showed high affinity for MBRs prepared from rat...
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abstract:BACKGROUND AND PURPOSE:Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects...
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abstract::1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials):...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0703092
更新日期:2000-02-01 00:00:00
abstract::1. We previously demonstrated that cyclopiazonic acid (CPA), an inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum, induced rhythmic relaxations of active tension in the endothelium-denuded small arteries of the mesentery and the ear of the rabbit, but that this agent failed to induce rhythmic responses in the e...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1996.tb15392.x
更新日期:1996-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1997-10-01 00:00:00
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更新日期:1983-07-01 00:00:00
abstract::1. The effect of frusemide, ethacrynic acid and indanyloxyacetic acid was investigated on spontaneous calcium-activated chloride (ICl(Ca)) and potassium currents (IK(Ca)) in rabbit portal vein cells with the perforated patch technique. 2. Frusemide (0.3-1.0 x 10(-3) M) reduced the amplitude of spontaneous transient in...
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更新日期:1999-12-01 00:00:00
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更新日期:1979-06-01 00:00:00
abstract::The platelet-lowering drug anagrelide inhibits bone marrow megakaryocytopoiesis by an unknown mechanism. Recently, it was found that anagrelide is bio-transformed in humans into two major metabolites (6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one (BCH24426) and 2-amino-5,6-dichloro-3,4,-dihydroquin...
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更新日期:2005-10-01 00:00:00
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更新日期:1993-01-01 00:00:00