Abstract:
:1 The effects of raising or lowering [Ca(2+)](o) or [Mg(2+)](o) on potential changes evoked by 5-hydroxytryptamine (5-HT) and by the nicotinic agonist, 1,1-dimethyl-4-phenyl piperazinium (DMPP) have been investigated.2 Changes in membrane potential were measured at the ganglion or in postganglionic axons by the sucrose-gap technique. The ganglionic response to both 5-HT and DMPP was a depolarization followed by an after-hyperpolarization (AH). AH decayed exponentially over most of its time course; the time constant of decay for 5-HT responses was 4.4 +/- 0.3 min (mean +/- s.e.mean, rate constant 0.23 min(-1)) and that for DMPP responses was not significantly different, being 3.9 +/- 0.3 min (rate constant 0.26 min(-1)).3 Increasing [Ca(2+)](o) to 5.1 or 7.6 mM caused some hyperpolarization of the ganglion, reduced the amplitude of depolarizations evoked by 5-HT by 29% and usually potentiated responses to DMPP (average 12%). Ca-free solutions caused a depolarization of the ganglion, increased the amplitude of depolarizations evoked by 5-HT by 23% and reduced that of depolarizations to DMPP by 32%. [Mg(2+)](o) 12.7 and 25.4 mM caused depolarizations of the ganglion and reduced the amplitude of depolarizations evoked by 5-HT by 34 and 84%, respectively, and those to DMPP by 10 and 75%, respectively. Mg-free solutions or low [Mg(2+)](o) caused a slow depolarization of the ganglion and reduced the amplitude of depolarizations to both 5-HT and DMPP by approx. 20%. Ca/Mg-free solutions produced a slow depolarization of the ganglion, increased the amplitude of depolarizations evoked by 5-HT by 78% and reduced those to DMPP by 58%.4 Increasing [Ca(2+)](o) reduced the amplitude of AH evoked by 5-HT by 50% and increased that to DMPP by 73%, while prolonging AH duration and increasing the time constant of decay. Ca-free solutions had complex effects on AH evoked by 5-HT, which were increased on average by 116%, and depressed AH evoked by DMPP; in both cases there was a decrease in the time constant of decay. [Mg(2+)](o) 12.7 mM reduced the amplitude of AH evoked by 5-HT more than that evoked by DMPP, and increased the rate of decline of the exponential phase. Low Mg solutions reduced in amplitude the AH evoked by 5-HT by 56% and the AH evoked by DMPP by 38%. The time constant of decay was increased. Ca/Mg-free solutions reduced AH amplitude in both 5-HT and DMPP responses. The effects on time constant are consistent with the generation of AH by an electrogenic sodium pump, the ATP-ase of which is Mg(2+)-dependent and inhibited by Ca(2+).5 Responses to 5-HT could be recorded from postganglionic axons and consisted of a rapid depolarization, sometimes followed by an AH whose time constant of decay was smaller than that of ganglionic responses. Full dose-response curves in control and test media could be obtained. In Ca/Mg-free solutions, 5-HT depolarizations were potentiated but no significant shift in the curve was observed.6 It is suggested that divalent cations modulate the coupling between 5-HT receptor and ion channel, an increase in [Ca(2+)](o) reducing the coupling or stabilizing the ion channel in the closed conformation. Ca(2+) and Mg(2+) may compete for the same binding site. This mechanism does not appear to be involved at nicotinic receptors and their related ion channels.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Nash HL,Wallis DIdoi
10.1111/j.1476-5381.1981.tb16813.xsubject
Has Abstractpub_date
1981-07-01 00:00:00pages
759-72issue
3eissn
0007-1188issn
1476-5381journal_volume
73pub_type
杂志文章abstract::1 Depolarizations were recorded intracellularly in smooth muscle from the taenia of the guinea-pig caecum in response to the iontophoretic application of acetylcholine, carbachol, oxotremorine-M, methylfurmethide, hexyl trimethylammonium and tetramethylammonium (TMA). 2 No differences between the iontophoretic respons...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb09131.x
更新日期:1981-02-01 00:00:00
abstract::We have examined whether modulation of the polyamine biosynthetic pathway, through inhibition by alpha-difluoromethylornithine (DFMO) of the rate limiting enzyme, ornithine decarboxylase (ODC), modulates NO synthesis in J774 macrophages. DFMO potentiated LPS-stimulated nitrite production in both a concentration- and t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702231
更新日期:1998-12-01 00:00:00
abstract::1. Changes induced in the electrocorticogram by the bilateral perfusion of (+)-amphetamine into the mesencephalic reticular formation (MRF) have been studied in cat encéphale isolé preparations. 2. (+)-Amphetamine, applied for 5 min in the MRF, mimicked the electrocortical desynchronization induced by the perfusion of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08424.x
更新日期:1977-11-01 00:00:00
abstract::The relaxin family peptides, although structurally closely related to insulin, act on a group of four G protein-coupled receptors now known as Relaxin Family Peptide (RXFP) Receptors. The leucine-rich repeat containing RXFP1 and RXFP2 and the small peptide-like RXFP3 and RXFP4 are the physiological targets for relaxin...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707140
更新日期:2007-03-01 00:00:00
abstract::1. Alterations of 5-hydroxytryptaminergic mechanisms are thought to play a special role in the pathogenesis of depression and antidepressant treatments are assumed to restore these changes. 2. We have used one of the most reliable models of depression, the olfactory bulbectomized rat to study the long term consequence...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701530
更新日期:1997-12-01 00:00:00
abstract::1. We investigated the nitric oxide (NO) dependence of vasorelaxation in response to different calcium channel blockers (CCB), in rabbit femoral artery in vivo. 2. Anaesthetized rabbits underwent femoral artery ligation, and blood from the proximal artery was returned distal to the ligature through a constant infusion...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704753
更新日期:2002-06-01 00:00:00
abstract::The uncoupling activity of oxyclozanide in warm blooded animals has been studied in whole animals, isolated tissue in vitro and on mitochondrial preparations. The onset of post mortem rigidity in mice and rats is accelerated and a contracture of striated muscle is produced. Oxyclozanide (1 muM) stimulated rat liver mi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09622.x
更新日期:1974-03-01 00:00:00
abstract::1. Neural crest material from neurula stage Xenopus embryos was tissue cultured as small aggregates of cells or a single cell suspension. Isolated pigment cells differentiated after 2 days in culture. 2. Melatonin (10(-15) to 10(-13) M) induced pigment granule condensation; it was 10,000 times more effective than any ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07554.x
更新日期:1977-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both dr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707680
更新日期:2008-04-01 00:00:00
abstract::1 A simple double-isotope assay for phospholipase A2 activity of perfused organs is described; Guinea-pig lungs perfused through the pulmonary circulation exhibit a low background enzyme activity. This activity is blocked by dexamethasone, betamethasone and hydrocortisone, mepacrine, procaine or chlorpromazine. Aspiri...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07009.x
更新日期:1978-01-01 00:00:00
abstract::Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased the production/secretion of immunoreactive endothelin (irET). Naturally occurring prostanoids and selective and non-selective EP receptor agonists showed the foll...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703886
更新日期:2001-03-01 00:00:00
abstract::1 Adenosine 5'-triphosphate (ATP) is an enteric neurotransmitter which acts at purine receptors on intestinal nerve and muscle. This study set out to shed light on the receptor mechanisms by which exogenous and endogenous ATP influences intestinal peristalsis. 2 Peristalsis in isolated segments of the guinea-pig small...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702808
更新日期:1999-09-01 00:00:00
abstract::1. We examined the effect of the sulphonylurea glimepiride on three types of recombinant ATP-sensitive potassium (K(ATP)) channels. 2. K(ATP) channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart and SUR2B in smooth mus...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704062
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) inhibitors are used in Parkinson's disease in which pain is an important symptom. COMT polymorphisms modulate pain and opioid analgesia in humans. In rats, COMT inhibitors have been shown to be pro-nociceptive in acute pain models, but also to attenuate allodyn...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2010-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates insulin biosynthesis and secretion in a glucose-dependent manner and has been reported to induce vasodilatation. Here, we examined the possible vasorelaxant effect of GLP-1 and its underlying mechanisms. EXPERIMENTAL APPROACH:...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14534
更新日期:2019-02-01 00:00:00
abstract::1. Idioventricular rate responses and adrenoceptor number have been examined in normal Langendorff hearts perfused at 70 cmH2O and in 'ischaemic' hearts perfused at 10 cmH2O. 2. In hearts perfused at normal pressure, ventricular rate responses to phenylephrine in the presence of propranolol were biphasic with low conc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb15860.x
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH:We assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13128
更新日期:2015-07-01 00:00:00
abstract::1 The effects of pretreatment with aspirin, and of prostacyclin (PGI(2)) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.2 Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb09359.x
更新日期:1983-01-01 00:00:00
abstract::The influence of endogenous and exogenous acidic amino acids on the binding of [3H]-MK-801, a selective, non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has been investigated in rat cerebral cortex crude synaptic membranes (CSM). Removal of endogenous glutamate and aspartate from CSM by repeated w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb10295.x
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Up-regulation of thioredoxin interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (Trx), compromises cellular antioxidant and anti-apoptotic defences and stimulates pro-inflammatory cytokines expression, implying a role for TXNIP in apoptosis. Here we have examined the causal role ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01336.x
更新日期:2011-09-01 00:00:00
abstract::Rabbit isolated hearts were perfused according to Langendorff with Tyrode solution. Prostaglandin-like substances (PLS) in the effluent were purified and assayed on the rat stomach strip Noradrenaline (NA) in the effluent was assayed fluorimetrically. 2 Infusion of nicotine (1 muM-50 muM) caused a dose-dependent, brie...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06981.x
更新日期:1977-01-01 00:00:00
abstract::1. The rate of gastric emptying was measured directly in 14 convalescent hospital patients and paracetamol absorption was studied following an oral dose of 1.5 g.2. Rapid gastric emptying was associated with the early appearance of high peak plasma paracetamol concentrations whereas peak concentrations were low and oc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08339.x
更新日期:1973-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Central anti-nociceptive actions of baclofen involve activation of K+ channels. Here we assessed what types of K+ channel might participate in the peripheral anti-nociception induced by baclofen. EXPERIMENTAL APPROACH:Nociceptive thresholds to mechanical stimulation in rat paws treated with intr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706898
更新日期:2006-11-01 00:00:00
abstract::1. Sodium nitroprusside, S-nitroso-N-acetyl-D,L-penicillamine, Spermine NONOate and DEA NONOate raised cyclic GMP levels in bovine chromaffin cells in a time and concentration dependent manner with different potencies, the most potent being DEA/NO with an EC50 value of 0.38 +/- 0.02 microM. 2. Measurements of NO relea...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702607
更新日期:1999-06-01 00:00:00
abstract::1. The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2. Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, biphasic responses: rapid trans...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705431
更新日期:2003-09-01 00:00:00
abstract::Experiments were undertaken to determine whether the site of the hypoglycaemic action of 5-hydroxytryptophan (5-HTP), a direct precursor of 5-hydroxytryptamine (5-HT), was in the central nervous system or in the liver. The fall in blood glucose followed the rapid increase in the amount of 5-HT both in the brain and li...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb10553.x
更新日期:1985-07-01 00:00:00
abstract::The neuroprotective drug riluzole has multiple effects on cellular signaling. We found that riluzole rapidly and reversibly inhibited spontaneous Ca2+ oscillations in both immortalized GnRH-secreting hypothalamic neurons (GT1 cells) and in the prolactin and growth-hormone-secreting GH3 cell line. At lower concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705491
更新日期:2003-11-01 00:00:00
abstract::1. Previous patch clamp studies of oesophageal circular muscle cells showed that nitric oxide (NO) modulated the opening of Ca2(+)-activated K+ channels involved in mediating the inhibitory junction potentials (i.j.ps). This study clarified the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in t...
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
abstract::1. [3H]-ouabain uptake in resting guinea-pig papillary muscles depended directly on incubation time and inversely with muscle radius. The equivalence of both parameters support the relevance of diffusion. A particular mechanism of receptor-controlled diffusion was implicated by the saturation of initial rates of uptak...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11659.x
更新日期:1988-10-01 00:00:00
abstract::1. Carrageenin or 5-hydroxytryptamine-induced oedema of the mouse hind paw was antagonized by catecholamines acting on both alpha- and beta-adrenoceptors.2. Increased permeability of the mouse peritoneum induced by the local injection of acetic acid or pro-inflammatory mediators was antagonized by catecholamines actin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb08086.x
更新日期:1972-06-01 00:00:00