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 electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric method and expressed as a mucus score which is inversely related to mucus discharge. 2. Morphine, 1 mg kg-1, completely blocked goblet cell secretion induced by electrical stimulation of the vagus nerves. Morphine also inhibited the response to cigarette smoke given either at a low dose (10 breaths of 1:10 diluted in air), which principally activates cholinergic nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin-sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had no significant inhibitory effect on capsaicin-induced goblet cell secretion. The inhibitory effect of morphine was reversed by naloxone. 3. Selective mu- or delta-opioid receptor agonists, [D-Ala2, NMePhe4, Glyol5]enkephalin (DAMGO) or [D-Pen2, D-Pen5]enkephalin (DPDPE) respectively, caused a dose-related inhibition of low dose cigarette smoke-induced goblet cell discharge, with DPDPE more potent than DAMGO. A kappa-receptor agonist, trans-3,4-dichloro-N-methyl-N-(2-(1-pyrollidinyl)cyclohexyl) benzeneacetamine (U-50,488H), had no inhibitory effect. DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous methacholine. 4. DAMGO dose-dependently blocked the response to high dose cigarette smoke with a maximal inhibition of 95% at 2 x 10(-7) mol kg-1. Neither DPDPE nor U-50,488H had any significant inhibitory effect. The increase in goblet cell secretion induced by exogenous substance P was not affected by DAMGO.5. We conclude that opioids inhibit neurally-mediated goblet cell secretion via actions at prejunctional delta and mu-receptors on cholinergic nerves and at mu-receptors on sensory nerve endings, and that capsaicin activation of sensory nerves is via a different mechanism from that of electrical or cigarette smoke activation.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kuo HP,Rohde JA,Barnes PJ,Rogers DFdoi
10.1111/j.1476-5381.1992.tb14259.xsubject
Has Abstractpub_date
1992-02-01 00:00:00pages
361-6issue
2eissn
0007-1188issn
1476-5381journal_volume
105pub_type
杂志文章abstract::1 The effects of general anaesthetics on the responses of neurones to iontophoretically applied L-glutamate have been examined in slices of the guinea-pig olfactory cortex in vitro. 2 Concentrations of pentobarbitone, ether, methoxyflurance, trichloroethylene and alphaxalone that are known to depress synaptic transmis...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::Since its discovery over 50 years ago, cAMP has been the archetypal second messenger introducing students to the concept of cell signalling at the simplest level. As explored in this review, however, there are many more facets to cAMP signalling than the path from Gs-coupled receptor to adenylyl cyclase (AC) to cAMP t...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01719.x
更新日期:2012-05-01 00:00:00
abstract::1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17101.x
更新日期:1994-11-01 00:00:00
abstract::1 We have investigated the effects of loperamide on intracellular Ca(2+) stores and membrane K(+) channels in insulin-secreting hamster insulinoma (HIT-T15) cells. 2 In cell-attached patch-clamp mode, loperamide (3-250 micro M) activated large single-channel currents. The loperamide-activated currents were tentatively...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705263
更新日期:2003-05-01 00:00:00
abstract::1. The pharmacological profile of LR-B/081, (methyl 2-[[4-butyl-2-methyl- 6-oxo-5-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1(6H)- pyrimidinyl]methyl]-3-thiophenecarboxylate), a novel antagonist at the angiotensin II (AII) AT1-receptor, was studied in vitro and in vivo. 2. In rabbit aortic strips incubated w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13323.x
更新日期:1995-03-01 00:00:00
abstract::A large range of neuroadaptations develop in response to chronic opioid exposure and these are thought to be more or less critical for expression of the major features of opioid addiction: tolerance, withdrawal and processes that may contribute to compulsive use and relapse. This review considers these adaptations at ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/bjp.2008.100
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13753
更新日期:2018-04-01 00:00:00
abstract::1. The effect of the calcitonin gene-related peptide antagonist (CGRP8-37, 400 nmol kg-1, i.v.) on the increased blood flow induced by calcitonin gene related peptide (CGRP), vasodilator prostaglandins, and topical capsaicin was measured with a laser Doppler blood flow meter in rat abdominal skin. 2. The saphenous ner...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13878.x
更新日期:1993-10-01 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...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704791
更新日期:2002-07-01 00:00:00
abstract::1. This study investigated the importance of renal sympathetic nerves in regulating sodium and water excretion from the kidneys of stroke prone spontaneously hypertensive and 2K1C Goldblatt hypertensive rats anaesthetized with chloralose/urethane (17.5/300 mg initially and supplemented at regular intervals), and prepa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15621.x
更新日期:1996-08-01 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
doi:10.1111/j.1476-5381.2010.01177.x
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Sepsis is a systemic inflammatory response accompanied by excessive production of inflammatory cytokines and cardiovascular dysfunction. Importantly, macrophage-derived pro-inflammatory agents play a key role in cardiovascular impairment in sepsis. Here we have investigated the effects of trimeta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13386
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:A putative novel cannabinoid receptor mediates vasorelaxation to anandamide and abnormal-cannabidiol and is blocked by O-1918 and by high concentrations of rimonabant. This study investigates VSN16, a novel water-soluble agonist, as a vasorelaxant potentially acting at non-CB1, non-CB2 cannabinoi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707470
更新日期:2007-11-01 00:00:00
abstract::The Mediterranean diet (MedDiet) is one of the most widely described and evaluated dietary patterns in scientific literature. It is characterized by high intakes of vegetables, legumes, fruits, nuts, grains, fish, seafood, extra virgin olive oil, and a moderate intake of red wine. A large body of observational and exp...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14778
更新日期:2020-03-01 00:00:00
abstract::1. The chemically novel acetohydroxamic acids, BW A4C, BW A137C and BW A797C, are potent inhibitors of the synthesis of leukotriene B4 (LTB4) from arachidonic acid by human leucocyte homogenates: the concentrations required for 50% inhibition (IC50) were 0.1 microM, 0.8 microM and 0.5 microM respectively. Inhibition w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11557.x
更新日期:1988-06-01 00:00:00
abstract::The peptides, neurotensin, substance P, somatostatin, and bombesin, several analogues and fragments of neurotensin and compound 48/80, all caused the secretion of both endogenous 5-hydroxytryptamine (5-HT) and histamine. There was no differential effect of any of the secretagogues tested on the secretion of 5-HT and h...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10069.x
更新日期:1984-02-01 00:00:00
abstract::1. We investigated the role of two conserved basic residues in the second transmembrane helix arginine 172 (R172) and lysine 179 (K179) of the VPAC(2) receptor. 2. Vasoactive intestinal polypeptide (VIP) activated VPAC(2) receptors with an EC(50) value of 7 nM, as compared to 150, 190 and 4000 nM at R172L, R172Q and K...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704195
更新日期:2001-08-01 00:00:00
abstract::Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, and one of the most common causes of disability in young adults. Over the last decade, new disease-modifying therapies have emerged, including monoclonal antibodies (mAbs) that provide highly targeted therapies with greater efficacy than platform th...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13780
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The Rho GTPase, Rac1, is involved in the pathogenesis of neuropathic pain induced by malformation of dendritic spines in the spinal dorsal horn (sDH) neurons. In the present study, the contribution of spinal Rac1 to peripheral inflammatory pain was studied. EXPERIMENTAL APPROACH:Effects of s.c. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13413
更新日期:2016-03-01 00:00:00
abstract::1. In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HT1A-receptor antagonists (S)WAY-100135 or WAY-100635 resulted in dose-dependent enhancement of the reflex responses of gastrocnemius motoneurones evoked by electrical stimulation of all myelinated afferents of the sura...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16019.x
更新日期:1996-11-01 00:00:00
abstract::The effects of high (20 mM) concentrations of caffeine were studied on the transmembrane voltage and currents in rat single ventricular myocytes by the whole cell configuration of the patch clamp technique. Rapid application of caffeine released Ca2+ from the sarcoplasmic reticulum and induced a Ni(2+)-sensitive trans...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13702.x
更新日期:1993-08-01 00:00:00
abstract::1 Administration of isoprenaline by aerosol inhalation to man results in over 80% being metabolized to the sulphate conjugate.2 The majority of an inhaled dose is probably swallowed since the metabolic pattern resembles that after an oral dose.3 Isoprenaline, administered in aqueous solution directly into the bronchia...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb08593.x
更新日期:1974-04-01 00:00:00
abstract::The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation,...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13532
更新日期:2017-06-01 00:00:00
abstract::1. Effects of indomethacin, the selective cyclo-oxygenase (COX)-2 inhibitors NS-398 and DFU, and dexamethasone on gastric damage induced by 30 min ischaemia followed by 60 min reperfusion (I-R) were investigated in rats. Modulation of gastric levels of COX-1 and COX-2 mRNA by I-R was evaluated using Northern blot and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702966
更新日期:1999-12-01 00:00:00
abstract::1. Pithed rats were respired at a fixed rate of 54 cycles min-1 and with a ventilation volume of either 20 (control) or 10 ml kg-1. In these two preparations, the dose-response relationships for the systemic blood pressure responses to endothelin-1, administered i.v., were examined. Also, cardiac output, its distribut...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb14638.x
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pyrazole derivatives have recently been suggested as selective blockers of transient receptor potential cation (TRPC) channels but their ability to distinguish between the TRPC and Orai pore complexes is ill-defined. This study was designed to characterize a series of pyrazole derivatives in term...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02126.x
更新日期:2012-12-01 00:00:00
abstract::1 In the isolated basilar artery of the rabbit, gamma-aminobutyrate acid (GABA) (ED50 +/- s.e. mean, 2.4 +/- 1.1 x 10(-5) M) produced a relaxation, if the tone had been increased with 5-hydroxytryptamine (5-HT). 2 3-Aminoproprane sulphonic acid (3-APS) produced a similar, but smaller relaxation, while baclofen had no ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08770.x
更新日期:1982-01-01 00:00:00
abstract::1. The rat isolated superior mesenteric bed, perfused with Krebs-Henseleit solution containing 10 microM indomethacin and precontracted with 100 microM methoxamine, was used to study the vasorelaxation produced by some fragments of endothelin-1, by two alanyl-substituted analogues, and by human and porcine proendothel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12428.x
更新日期:1991-10-01 00:00:00
abstract::Excessive death of cardiac myocytes leads to many cardiac diseases, including myocardial infarction, arrhythmia, heart failure and sudden cardiac death. For the last several decades, most work on cell death has focused on apoptosis, which is generally considered as the only form of regulated cell death, whereas necros...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14363
更新日期:2019-11-01 00:00:00
abstract::1. It has been reported previously that the milrinone analogues, ethyl 5-cyano-1,6-dihydro-2-methyl-6-oxo-3 pyridine carboxylate (I) and ethyl 5-cyano-1,6-dihydro-2-ethyl-6-oxo-3 pyridine carboxylate (II) exert a positive inotropic effect (EC50 = 15.6 +/- 0.2 microM and 40.3 +/- 0.1 microM) both on spontaneously beati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12519.x
更新日期:1991-12-01 00:00:00