Abstract:
:1. The effects of NS 1619, the putative BKCa channel opener, were investigated on rat intact portal veins and on single smooth muscle cells enzymatically separated from the same tissue. 2. Under whole-cell patch clamp conditions with K-rich pipettes, exposure of single cells held at -10 mV to NS 1619 (10-33 microM) induced a noisy, outward current which reached a maximum (33 microM NS 1619; mean 35.8 +/- 17 pA, n = 8) within about 6 min. 3. On stepping to test potentials (range -50 to +50 mV) from a holding potential of -10 mV, the NS 1619-induced noisy current exhibited time-dependent activation and marked outward rectification. 4. The stimulation of outward currents by NS 1619 at -10 mV was independent of the presence of Ca2+ in the bath or pipette solutions but was antagonized by either charybdotoxin (250 nM) or penitrem A (100 nM) in the bath solution. 5. Stationary fluctuation analysis of the noisy current induced by NS 1619 at -10 mV yielded a value of 70 +/- 8 pS (n = 4) (under the quasi-physiological conditions of the experiment) for the unitary conductance of the channel involved. 6. At -10 mV, NS 1619 (10-33 microM) rapidly inhibited spontaneous transient outward currents. 7. With a holding potential of -90 mV, NS 1619 (10-33 microM) produced a reduction of outward currents evoked by depolarizing steps to +50 mV, an effect associated with marked inhibition of the delayed rectifier current, IK(V). 8. NS 1619 (3-100 microM) produced a concentration-dependent inhibition of spontaneous activity in rat portal vein characterized by a reduction in the amplitude and duration of the tension waves. This inhibition was slightly potentiated in the presence of either charybdotoxin (250 nM) or penitrem A (1 microM). NS 1619 also totally inhibited contractions of rat aorta induced by KCl (both 20 mM and 80 mM). 9. Under whole-cell recording conditions and using Cs-rich pipettes, Ca-currents evoked in portal vein cells by stepping from a holding potential of - 90 mV to test potentials in the range - 30 to + 50 mV were totally inhibited in the presence of 33 JAM NS 1619.10. NS 1619 (33 JAM) inhibited the induction of IK(ATP) by levcromakalim (10 JAM).11. It is concluded that NS 1619 activates the large conductance, Ca2+-sensitive channel, BKca and over the same concentration range it inhibits both KV and L-type Ca-channels. The observed NS 1619-induced mechanical inhibition in rat portal vein and aorta seems most likely to be due to the observed inhibition of Ca-currents.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Edwards G,Niederste-Hollenberg A,Schneider J,Noack T,Weston AHdoi
10.1111/j.1476-5381.1994.tb17171.xsubject
Has Abstractpub_date
1994-12-01 00:00:00pages
1538-47issue
4eissn
0007-1188issn
1476-5381journal_volume
113pub_type
杂志文章abstract::Growing evidence suggests that interleukin (IL)-13, a Th2-type cytokine, plays a critical role in the development of bronchial hyper-responsiveness (BHR), an essential feature of asthma, although the underlying mechanisms remain unknown. In the present study, we investigated whether IL-13 directly affects airway smoot...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0705558
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abstract:BACKGROUND AND PURPOSE:This study investigated the role of central sympathetic activity and related mitogen-activated protein kinase (MAPK) signalling in the cardiovascular effects of ethanol in a model of acute renal failure (ARF). EXPERIMENTAL APPROACH:The effects of pharmacological interventions that inhibit periph...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.2009.00444.x
更新日期:2009-11-01 00:00:00
abstract::1. The effects of a series of nine GABAB receptor antagonists of widely varying potencies on electrically stimulated release from cortical slices of [3H]-GABA in the absence or presence of 10 microM of the GABAB agonist, (-)-baclofen and of endogenous glutamate in the presence of (-)-baclofen were compared. 2. The con...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1994.tb17168.x
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abstract::1. In circular smooth muscle of the guinea-pig gastric fundus, transmural nerve stimulation evoked a cholinergic excitatory junction potential (e.j.p.), and blockade of the e.j.p. by atropine revealed a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (i.j.p.). 2. The amplitude of the e.j.p. was inc...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1996.tb15290.x
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abstract::Multiple myeloma is a neoplastic disorder of plasma cells characterized by clonal proliferation within the bone marrow. One of the major clinical features of multiple myeloma is the destructive osteolytic bone disease that occurs in the majority of patients. Myeloma bone disease is associated with increased osteoclast...
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abstract::1. We have determined which cytokines induce and modulate the production of the chemokine interleukin-8 (IL-8) by the human colonic epithelial cell line HT-29. 2. Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin-1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF-alpha...
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更新日期:1973-02-01 00:00:00
abstract::1. ICI D7114 is a novel, beta-adrenoceptor agonist which stimulates whole body oxygen consumption in conscious rats, cats and dogs and brown adipose tissue (BAT) activity in conscious rats. Treatment of rats with ICI D7114 stimulated oxygen consumption (ED50, 0.04 mg kg-1, p.o.) and BAT mitochondrial guanosine diphosp...
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abstract:BACKGROUND AND PURPOSE:We sought to understand why (-)-cannabidiol (CBD) and (-)-cannabidiol-dimethylheptyl (CBD-DMH) exhibit distinct pharmacology, despite near identical structures. EXPERIMENTAL APPROACH:HEK293A cells expressing either human type 1 cannabinoid (CB1 ) receptors or CB2 receptors were treated with CBD ...
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