Abstract:
:1. Previous studies suggested that nitric oxide (NO) may cause hyperpolarization and relaxation of canine colonic smooth muscle by both cGMP-dependent and cGMP-independent mechanisms. This hypothesis was tested using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a novel inhibitor of NO-stimulated guanylate cyclase. 2. In the presence of histamine (30 microM), atropine and indomethacin (both at 1 microM), electrical field stimulation of intrinsic neurons (EFS; 5 Hz) produced inhibition of phasic contractile activity that is due to NO synthesis. ODQ caused a concentration-dependent block of this response (10 nM to 10 microM). 3. Inhibitory junction potentials (IJPs) due to NO synthesis were recorded from muscle cells located near the myenteric border of the circular muscle layer, using intracellular microelectrodes. IJPs were abolished by ODQ (1-10 microM). 4. EFS (10-20 Hz) produced frequency-dependent inhibition of electrical slow waves recorded from cells located near the submucosal surface of the circular muscle layer. This inhibition is due to NO synthesis, and it was abolished by ODQ (1-10 microM). 5. Hyperpolarization and relaxation produced by an NO donor, sodium nitroprusside, were abolished by ODQ pretreatment (1-10 microM). In contrast, inhibitory responses to 8-Br-cGMP (1 mM) were unaffected by ODQ. 6. ODQ alone (1-10 microM) had no significant effect on spontaneous electrical or phasic contractile activity. In tissues pre-treated with L-NAME (300 microM), ODQ decreased the amplitude of spontaneous or histamine-stimulated phasic contractile activity. 7. These results suggest that electrical and mechanical effects of endogenously released and exogenously applied NO in canine colon are largely due to cGMP synthesis by ODQ-sensitive soluble guanylate cyclase. No evidence to support a direct (cGMP-independent) mechanism of NO action was found. ODQ also appears to cause a non-specific inhibition of muscle contractile activity; however, this effect does not contribute to block of NO-dependent effects.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Franck H,Sweeney KM,Sanders KM,Shuttleworth CWdoi
10.1038/sj.bjp.0701487subject
Has Abstractpub_date
1997-11-01 00:00:00pages
1223-9issue
6eissn
0007-1188issn
1476-5381journal_volume
122pub_type
杂志文章abstract::1. Salmeterol, a novel, long-acting beta-adrenoceptor agonist, has been compared with isoprenaline and salbutamol for activity in vitro on a range of beta-adrenoceptor containing preparations from laboratory animals and man, and in vivo for bronchodilator activity in the conscious guinea-pig. 2. Salmeterol, like isopr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12486.x
更新日期:1991-11-01 00:00:00
abstract::1. Measurements were made of the uptake, metabolism and release of [(3)H]-adrenaline by human platelets in citrated plasma or in an artificial medium.2. Radioactive adrenaline was not taken up at 0-2 degrees C. At 37 degrees C there was a slow uptake which continued for at least 5 hours.3. About half of the radioactiv...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09903.x
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08184.x
更新日期:1973-03-01 00:00:00
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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更新日期:2002-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10889.x
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pub_type: 杂志文章
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更新日期:1993-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15151.x
更新日期:1996-01-01 00:00:00
abstract::1. Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADP-ribose) polymerase (PARP) is beneficial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704185
更新日期:2001-08-01 00:00:00
abstract::Along with many other mammalian ATP-binding cassette (ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding proteins ranging from 638 to 678 amino acids in length. All f...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2011-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08955.x
更新日期:1985-11-01 00:00:00
abstract::1. N-methyl-gamma-aminobutyrate (N-methylGABA), N-methylglycine, N-methyltaurine and N-methylbeta-alanine diminished the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Usually a weak excitatory effect preceded the inhibition. 2. The inhibitory effects of N-methylGABA and N-methylbeta-alanin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07720.x
更新日期:1977-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechan...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.119
更新日期:2008-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705453
更新日期:2003-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12899
更新日期:2015-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14877.x
更新日期:1994-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15280.x
更新日期:1996-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15327.x
更新日期:1996-04-01 00:00:00
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更新日期:2004-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb08723.x
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1989.tb12682.x
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abstract::1 Atrial pacing at progressively increasing frequencies was performed on unanaesthetized dogs through electrodes placed aseptically in the wall of the right atrium and exteriorized in the neck region. 2 Heart rate and two atrioventricular conduction (AVC) parameters, namely the Wenckebach Point (one or two systole blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09300.x
更新日期:1982-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705303
更新日期:2003-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0703356
更新日期:2000-06-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1994.tb13050.x
更新日期:1994-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The locus coeruleus (LC) is a major source of noradrenergic projections to the dorsal spinal cord, and thereby plays an important role in the modulation of nociceptive information. The LC receives inputs from substance P (SP)-containing fibres from other regions, and expresses the NK(1) tachykin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01820.x
更新日期:2012-06-01 00:00:00
abstract::The diterpene, forskolin, is shown to produce a concentration-dependent, increase in short circuit current in two epithelial preparations, amphibian skin and rat colon. In the amphibian tissue the increase is sensitive to amiloride and due to an increase in electrogenic transepithelial sodium transport towards the ser...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1982-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The human kinome consists of roughly 500 kinases, including 150 that have been proposed as therapeutic targets. Protein kinases regulate an array of signalling pathways that control metabolism, cell cycle progression, cell death, differentiation and survival. It is not surprising, then, that new ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14062
更新日期:2017-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704700
更新日期:2002-05-01 00:00:00
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更新日期:2000-03-01 00:00:00