Abstract:
:1. In order to investigate the vasodilator mechanisms of the K+ channel openers, cromakalim, pinacidil and nicorandil, we measured changes in cytoplasmic Ca2+ concentration [( Ca2+]i) simultaneously with force by a microfluorimetric method using fura-2, a calcium indicator, in canine coronary arterial smooth muscle cells. 2. The three K+ channel openers all produced a concentration-dependent reduction of [Ca2+]i in 5 and 30 mM KCl physiological salt solution (PSS) but failed to affect [Ca2+]i in 45 and 90 mM KCl-PSS. 3. Cromakalim only partly inhibited (-45%) the 30 mM KCl-induced contractures, whereas pinacidil and nicorandil nearly abolished contractions produced by 45 mM, 90 mM and 30 mM KCl-PSS. 4. Tetrabutylammonium (TBA), a nonselective K+ channel blocker, or glibenclamide, a supposed adenosine 5'-triphosphate (ATP)-sensitive K+ channel blocker, abolished the reduction of [Ca2+]i caused by the three K+ channel openers and the relaxant effect of cromakalim, whereas they only slightly attenuated the relaxant effects of pinacidil and nicorandil. 5. The increase in [Ca2+]i produced by 45 or 90 mM KCl-PSS in the presence of pinacidil or nicorandil was abolished by 10(-5) M verapamil, indicating that the increase in [Ca2+]i was caused by the influx of extracellular Ca2+ and that pinacidil and nicorandil did not affect the voltage-dependent Ca2+ channel directly. 6. The [Ca2+]i-force relationship in the presence of cromakalim was not distinguishable from that of control. 7. The [Ca2+]i-force curve was shifted to the right by pinacidil and nicorandil. 8. These results show that cromakalim is a more specific K+ channel opener than pinacidil and nicorandil, and that vasodilatation produced by cromakalim in this study is predominantly a result of a reduction of [Ca2+]i due to the closure of voltage-dependent Ca21 channels by hyperpolarization. In contrast, additional mechanisms are involved in the vasodilator actions of pinacidil and nicorandil. One of these is related to a reduction in the sensitivity of contractile proteins to Ca2 . The latter mechanism of nicorandil is akin to that of nitroglycerin. K+ channels opened by these K+ channel openers may be ATP-sensitive ones which are blocked by glibenclamide.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Yanagisawa T,Teshigawara T,Taira Ndoi
10.1111/j.1476-5381.1990.tb12106.xsubject
Has Abstractpub_date
1990-09-01 00:00:00pages
157-65issue
1eissn
0007-1188issn
1476-5381journal_volume
101pub_type
杂志文章abstract::1. Mild stress plus mild pain (solvent injection) applied daily to neonatal mice induces hormonal, behavioural and metabolic changes perduring in the adult life. 2. We investigated whether daily mild stress to neonatal mice induces also long-term defined changes of immune response, and whether immune changes are preve...
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1975.tb07620.x
更新日期:1975-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Fatty acid amide hydrolase inhibitors show promise as a treatment for anxiety, depression and pain. Here we investigated whether perinatal exposure to URB597, a fatty acid amide hydrolase inhibitor, alters brain development and affects behaviour in adult mice. EXPERIMENTAL APPROACH:Mouse dams we...
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