Abstract:
:1. Inflammatory diseases of the pancreas or diseases which cause obstruction within the biliary or within the biliary or pancreatic duct system are associated with severe pain. Although neuropeptides such as substance P are present in the biliary tree, only few capsaicin-sensitive, substance P-positive nerve fibres have been found in the ducts. In order to obtain functional evidence whether capsaicin-sensitive afferent neurones transmit nociceptive information arising from the biliopancreatic duct, blood pressure reflexes following electrical stimulation of the duct or increases in intraductal pressure were determined in barbiturate-anaesthetized rats. 2. Electrical stimulation of neurones in the biliopancreatic duct was carried out at 30 V, 3 ms, 50 Hz for 20s. In untreated animals the electrical stimulation resulted in rises in blood pressure by up to 25 mmHg, but in about a quarter of all animals tested this response was absent. Following the administration of phentolamine (7 mumol kg-1, i.p.) the blood pressure responses were changed to pronounced and reproducible depressor reflexes of -5 to -30 mmHg. Retrograde injections into the biliopancreatic duct of 300 microliters of a 154 mM sodium chloride solution produced increases in intraductal pressure of approximately 10 mmHg. This elicited shortlasting falls in blood pressure of 3-15 mmHg. Phentolamine significantly augmented the fall in blood pressure to 8-30 mmHg. 3. The depressor reflexes observed in both models after the administration of phentolamine were abolished by morphine (1 mumol kg-1, i.v.). The inhibition by morphine was reversed by naloxone (3 mumol kg-1, i.v.). Naloxone given before morphine did not affect the depressor reflex but prevented the inhibitory action of subsequently injected morphine.4. Acute s.c. injection of capsaicin (30 mg kg-1) abolished the depressor reflexes in response to both types of nociceptive stimulation in phentolamine-treated rats. The initial pressor effects of electrical stimulation were only partly inhibited by capsaicin whereas the basal depressor reflexes in response to elevation of intraductal pressure were abolished. In rats which had received capsaicin on the day before the experiment or had been treated with capsaicin as neonates, only minor rises in blood pressure were induced by electrical stimulation at the beginning of the experiment and no changes in blood pressure occurred after the administration of phentolamine. After adult or neonatal pretreatment with capsaicin the depressor reflexes in response to increased intraductal pressure were only small and were unchanged by phentolamine.5. The depressor reflexes following either electrical stimulation or increases in intraductal pressure were abolished by the unselective Beta-blocker, (-)-propranolol (3 micromol kg-1, i.p.), and greatly reduced by the Beta 1-blocker, metoprolol (6 micromol kg- 1, i.p.). The Beta2-preferring adrenoceptor antagonist, butoxamine(3 micromol kg-1, i.p.), had no effect on the depressor responses. The reflex falls in blood pressure were also abolished by hexamethonium (10 micromol kg-1, i.p.) but not by atropine (3 micromol kg-1, i.p.).6. Both models of stimulation of nociceptive afferents caused identical patterns of blood pressure responses following adrenalectomy or chemical sympathectomy. In adrenalectomized rats, the initial responses consisted of depressor reflexes which were not augmented but significantly reduced by phentolamine and further inhibited by metoprolol. In rats that had been pretreated with 6-hydroxydopamine(total dose 0.6 mmol kg-1) to accomplish chemical sympathectomy, nociceptive stimulation caused rises in blood pressure. Phentolamine treatment abolished these pressor effects but revealed only minor, if any, depressor responses that were unaffected by metoprolol.7. In summary, the hypotensive effects in both models constitute nociceptive reflexes since they are abolished by morphine and restored by naloxone. The afferent part of the reflex is mediated by nerve fibres sensitive to capsaicin. Both experimental procedures seem to elicit two, presumably separate, reflex mechanisms. Firstly, catecholamines released from the adrenal medulla elevate blood pressure or limit hypotensive responses via activation of vascular alpha receptors. Secondly, the reflex inhibition of the sympathetic nerve activity in the heart and the vasculature causes the nociceptive depressor reflexes.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Griesbacher Tdoi
10.1111/j.1476-5381.1994.tb14772.xsubject
Has Abstractpub_date
1994-02-01 00:00:00pages
547-54issue
2eissn
0007-1188issn
1476-5381journal_volume
111pub_type
杂志文章abstract::This paper is intended to assist pharmacologists to make the most of statistical analysis and avoid common errors. A scenario, in which an experimenter performed an experiment in two separate stages, combined the control groups for analysis and found some surprising results, is presented. The consequences of combined ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2008-11-01 00:00:00
abstract::1. To see if arachidonic acid (AA) plays a role in the sustained suppression of voltage-gated calcium channel currents produced by muscarinic receptor stimulation by carbachol (CCh), the effects of AA on membrane currents were examined in whole-cell voltage-clamped smooth muscle cells of the guinea-pig ileum. 2. In ce...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1996.tb15973.x
更新日期:1996-09-01 00:00:00
abstract::Ouabain was administered at a loading dose of 3 mug/kg followed by an infusion at a rate of 1 mug/kg-1 min-1 in order to produce severe dysrhythmia in dogs within 60 minutes. Similarly, digitoxin at a loading dose of 9 mug/kg followed by an infusion at a rate of 3 mug kg-1 min-1 was administered to compare its effect ...
journal_title:British journal of pharmacology
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更新日期:1977-01-01 00:00:00
abstract::1. The purpose of this study was to determine the in vivo inhibitory efficacy of azapropazone on neutrophil migration. The effects of azapropazone given at a dose of 100 mg kg-1 i.v. every 2 h on the neutrophil migration into skin inflammation sites (blister fluid) as well as into an autologous serum (+/- chemoattract...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1990.tb14686.x
更新日期:1990-02-01 00:00:00
abstract::1. Adenosine A(1), A(2A), and A(3) receptors (ARs) and extracellular signal-regulated kinase 1/2 (ERK1/2) play a major role in myocardium protection from ischaemic injury. In this study, we have characterized the adenosine receptor subtypes involved in ERK1/2 activation in newborn rat cardiomyocytes. 2. Adenosine (non...
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11486.x
更新日期:1988-04-01 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.tb15661.x
更新日期:1996-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701739
更新日期:1998-03-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14864.x
更新日期:1994-04-01 00:00:00
abstract::1. Electrically-evoked contractions in different regions of the rabbit isolated pulmonary artery have been investigated using stimulation parameters generally assumed to stimulate nerves selectively. 2. In extrapulmonary artery, trains of stimuli (10 Hz; pulse width 0.1 ms) evoked monophasic contractions. In contrast,...
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doi:10.1038/sj.bjp.0704863
更新日期:2002-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Allosteric modulators of ionotropic receptors and GPCRs might constitute valuable therapeutic tools for intervention in several diseases, including Parkinson's disease (PD). However, the possibility that some of these compounds could alter neurotransmission in health and disease has not been thor...
journal_title:British journal of pharmacology
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doi:10.1111/bph.12758
更新日期:2014-08-01 00:00:00
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doi:10.1038/sj.bjp.0705713
更新日期:2004-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08184.x
更新日期:1973-03-01 00:00:00
abstract::Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonar...
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journal_title:British journal of pharmacology
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pub_type: 杂志文章
doi:10.1038/bjp.2008.71
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The sonic hedgehog pathway (Shh) plays a central role in maintaining stem cell function and behaviour in various processes related to self-renewal and tissue regeneration. However, the therapeutic effect of Shh on mouse embryonic stem cells (mESCs) has not yet been clearly elucidated. Thus, we in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14423
更新日期:2018-09-01 00:00:00
abstract::1. Milacemide is a glycine prodrug which is both an inhibitor and a substrate for monoamine oxidase-type B (MAO-B) and also an inhibitor of MAO-type A (MAO-A). Its effects on dopamine and 5-hydroxytryptamine (5-HT) metabolism in rat frontal cortex tissue and dialysate were evaluated. 2. Dialysate dopamine concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14210.x
更新日期:1992-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb14897.x
更新日期:1995-01-01 00:00:00
abstract::1. The potential influences of nitric oxide (NO) and prostaglandins on the renal effects of angiotensin II (Ang II) have been investigated in the captopril-treated anaesthetized rat by examining the effect of indomethacin or the NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), on the renal respo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702003
更新日期:1998-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703330
更新日期:2000-06-01 00:00:00
abstract::1. Modulation by nitric oxide (NO) of the ATP-sensitive K+ channel (KATP) current (IK(ATP)) was investigated in single ventricular cells dissociated from guinea-pig hearts. IK(ATP) was induced by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine+ ++ (KRN4884) and cromakalim. 2. In the whole-cell pat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701069
更新日期:1997-04-01 00:00:00
abstract::1. The interactions between N-methyl-D-aspartate (NMDA) and metabotropic glutamate receptors (mGluRs) were investigated in striatal slices, by utilizing intracellular recordings, both in current- and voltage-clamp mode. 2. Bath-application (50 microM) or focal application of NMDA induced a transient membrane depolariz...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0700999
更新日期:1997-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706900
更新日期:2006-12-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1988.tb11657.x
更新日期:1988-10-01 00:00:00