Abstract:
:1. The effects of nipradilol, a beta-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+]i), and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries. 2. Nipradilol reduced in a concentration-dependent manner both the [Ca2+]i and tension, irrespective of whether the strips were unstimulated or exposed to either high K+ or histamine containing solutions. However, both in the case of contractions induced by high K+-depolarization and histamine stimulation, for a given [Ca2+]i elevation the tension which developed in the presence of nipradilol was smaller than that generated in its absence, so that the [Ca2+]i-tension curves during the contraction were shifted to the right. 3. In the absence of extracellular Ca2+, the [Ca2+]i elevation due to the release of Ca2+ from histamine-sensitive store was inhibited by nipradilol. Nipradilol had no effect on the [Ca2+]i elevation due to the release of Ca2+ from caffeine-sensitive stores; however, it did inhibit the caffeine-induced increase in tension. A derivative of nipradilol, which lacked a nitroxy molecule (Nip(-N)), had no effect on the [Ca2+]i and tension elevated by histamine or caffeine in the absence of extracellular Ca2+. 4. The beta-adrenoceptor agonist, isoprenaline, reduced [Ca2+]i tension when applied to steady state contractions induced by high K+, or at the peak level of tension to histamine. The reduction of [Ca2+]i and tension induced by isoprenaline was inhibited by Nip(-N) in a concentration-dependent manner and nipradilol inhibited the isoprenaline-induced relaxation with bell-shaped concentration-response curves. At lower concentrations, nipradilol acted as a beta-blocker, the IC50- value being smaller than that of Nip(-N), and at higher concentrations, it acted as a nitrovasodilator. 5. Thus, it is suggested that, at lower concentrations, nipradilol, an antianginal drug, acts as a beta-adrenoceptor antagonist. At higher concentrations, it relaxes the proximal portion of the coronary artery by directly reducing [Ca2+]i and the Ca2+-sensitivity of the myofilaments, apparently due to the presence of the nitroxy molecule.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Abe S,Nakamura M,Kanaide Hdoi
10.1111/j.1476-5381.1996.tb15343.xsubject
Has Abstractpub_date
1996-04-01 00:00:00pages
1707-15issue
8eissn
0007-1188issn
1476-5381journal_volume
117pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Humanized mice for the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ), termed PPARδ knock-in (PPARδ KI) mice, were generated for the investigation of functional differences between mouse and human PPARδ and as tools for early drug efficacy assessment. EXPERIMENTAL APPROACH...
journal_title:British journal of pharmacology
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abstract::1. Alterations of 5-hydroxytryptaminergic mechanisms are thought to play a special role in the pathogenesis of depression and antidepressant treatments are assumed to restore these changes. 2. We have used one of the most reliable models of depression, the olfactory bulbectomized rat to study the long term consequence...
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abstract::1. The effects of dopamine on the L-type Ca2+ current (ICa,L) of both atrial and ventricular single myocytes and on the force of contraction of atrial trabeculae in rat heart were investigated. 2. Dopamine increased atrial ICa,L at concentrations higher than 1 microM, but had little or no effect on ICa,L at lower conc...
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1971.tb07109.x
更新日期:1971-06-01 00:00:00
abstract::1. We have investigated pre- and post-junctional responsiveness in vas deferens from wild-type and alpha(2A/D)-adrenoceptor knockout mice. The response to a single stimulus was not significantly different between wild-type and knock-out mice. The isometric contraction to 10 Hz stimulation for 4 s was significantly lar...
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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journal_title:British journal of pharmacology
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doi:10.1111/bph.13255
更新日期:2015-10-01 00:00:00
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abstract::1. Goblet cell secretion in guinea-pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea-pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrica...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1992.tb14259.x
更新日期:1992-02-01 00:00:00
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abstract::1. This study was done to characterize the influence of calcium channel blockade on renin secretion and renin gene expression in normal rats and rats with renovascular hypertension. To this end we studied the effects of the 1,4-dihydropyridine derivative, amlodipine, on plasma renin activity and renal renin m-RNA leve...
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doi:10.1111/j.1476-5381.1996.tb15735.x
更新日期:1996-10-01 00:00:00
abstract::1. We assessed the relaxant effect of 17 beta-oestradiol (10(-7), 10(-6) and 10(-5) M) on rabbit isolated coronary arteries precontracted with prostaglandin F2 alpha (3 x 10(-6) M), high extracellular potassium (30 mM) and Bay K 8644 (10(-6) M) plus high extracellular potassium (15 mM) by measuring isometric tension. ...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1973.tb08321.x
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abstract::Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, is activated by several compounds, including the thiazolidinediones. In addition to being a therapeutic target for obesity, hypolipidaemia and diabetes, perturbation of PPARgamma signalling is now believed to be...
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