Abstract:
:1. Catecholamine release from cat adrenal glands perfused at a high rate (4 ml min-1) at 37 degrees C with modified Krebs solutions lacking Ca and containing 1.2 mM K (hyperpolarizing solution) or 118 mM K (depolarizing solution) was triggered by 10-s pulses of Ca (0.5 mM) in the presence of 118 mM K. Hyperpolarized glands released 1280 +/- 135 ng per pulse and depolarized glands 831 +/- 98 ng per pulse (n = 29). 2. While the dihydropyridine Ca channel blocker nitrendipine inhibited secretion in hyperpolarized glands with an IC50 of 214 nM, in depolarizing conditions the drug was much more potent (IC50 = 0.99 nM). In contrast, the inorganic Ca channel blocker cadmium inhibited secretion with the same potency both in hyperpolarized or depolarized glands. 3. Cinnarizine, diltiazem and verapamil exhibited intermediate degrees of voltage-dependence in blocking secretion. The IC50 ratios between hyperpolarized and depolarized glands were 215, 36, 19, 8 and 0.76 respectively for nitrendipine, cinnarizine, diltiazem, verapamil and cadmium. Because the experimental design (strong depolarization in the absence of Ca) favours the highest opening probability of Ca channels, it seems that these drugs bind preferentially to their receptors when these channels are in their open state. 4. Variable voltage-dependent effects of the five Ca channel blockers on adrenomedullary catecholamine release suggests different sites and mechanisms of action on, or near L-type Ca channels in chromaffin cells. In addition, these findings might help to explain why these drugs exhibit tissue selectivity and why they act differently in normal polarized as compared to ischaemic depolarized cells.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
López MG,Moro MA,Castillo CF,Artalejo CR,García AGdoi
10.1111/j.1476-5381.1989.tb11874.xsubject
Has Abstractpub_date
1989-03-01 00:00:00pages
725-31issue
3eissn
0007-1188issn
1476-5381journal_volume
96pub_type
杂志文章abstract::1. Openers of ATP-sensitive K(+) channels are of interest in several therapeutic indications including overactive bladder and other lower urinary tract disorders. This study reports on the in vitro and in vivo characterization of a structurally novel naphthylamide N-[2-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705908
更新日期:2004-09-01 00:00:00
abstract::Botulinum toxin (Type A) depressed or abolished transmission from postganglionic nerves to smooth muscle of isolated preparations of guinea-pig and mouse vas deferens. The time course of blockade was 2 to 6 times slower than that observed with the same concentration of the same batch of toxin on the rat diaphragm. Spo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08343.x
更新日期:1973-02-01 00:00:00
abstract::1 The specific stimulating action of dopamine and L-DOPA on exocrine pancreatic secretion was further investigated in the isolated blood-perfused canine pancreas.2 6-Hydroxydopamine (100 mug, i.a.) stimulated the secretion but was far less potent than dopamine. Epinine (0.3-1 mg. i.a.), alpha-methyldopamine (10-300 mu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09651.x
更新日期:1974-06-01 00:00:00
abstract::(1) Rapid desensitization of ligand-gated ion channel receptors can alter the apparent activity of receptor modulators, as well as make detection of fast-channel activation difficult. Investigation of the antagonist pharmacology of ATP-sensitive homomeric P2X3 receptors is limited by agonist-evoked fast-desensitizatio...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0705411
更新日期:2003-09-01 00:00:00
abstract::1 New 2H-1,4-benzoxazine derivatives were synthesized and tested for their agonist properties on the ATP-sensitive K(+) channels (K(ATP)) of native rat skeletal muscle fibres by using the patch-clamp technique. The novel modifications involved the introduction at position 2 of the benzoxazine ring of alkyl substituent...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0705233
更新日期:2003-05-01 00:00:00
abstract::1. We have shown earlier that pilocarpine strongly inhibits mouse and human liver coumarin 7-hydroxylase activity of CYP 2A and pentoxyresorufin O-deethylase activity of CYP 2B in vitro. Since pilocarpine, like coumarin, contains a lactone structure we have studied in more detail its inhibitory potency on mouse and hu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb17217.x
更新日期:1995-11-01 00:00:00
abstract::1. When injected intraperitoneally into mice in doses larger than those used clinically, all the amino derivatives of bisphosphonates (aminoBPs) tested induce a variety of inflammatory reactions such as induction of histidine decarboxylase (HDC, the histamine-forming enzyme), hypertrophy of the spleen, atrophy of the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702367
更新日期:1999-02-01 00:00:00
abstract::1. The effect of central injection of selective kinin B1 and B2 receptor antagonists on the febrile response induced by endotoxin (E. coli lipopolysaccharide, LPS) in rats was investigated. 2. Intracerebroventricular (i.c.v.) injection of a selective B2 receptor antagonist (Hoe-140, 8 nmol) reduced the early (0-2 h), ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701110
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Abdominal aortic aneurysm (AAA) is a degenerative disease with irreversible and progressive dilation of the artery. But there are few options for efficacious treatment except for traditional surgery. Probucol has been widely applied to treat hyperlipidaemia and atherosclerosis in clinic, but whet...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14857
更新日期:2020-01-01 00:00:00
abstract::1. The role of both exogenously administered and endogenously generated bradykinin (BK) on LPS-induced eosinophil accumulation in the mice pleural cavity was investigated by means of treatment with BK selective receptor agonists/antagonists and captopril. 2. Intrathoracic (i.t.) injection of LPS (250 ng cavity(-1)) in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702567
更新日期:1999-05-01 00:00:00
abstract::1 The influence of the external calcium concentration on the effect of harmine 2 x 10(-5) M upon the guinea-pig atrial muscle was analysed. Transmembrane potentials of contractile fibres were measured during exposure to the drug at 30 degrees C. 2 In preparations superfused with 1.35 mM Ca2+-Tyrode solution and driven...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb09986.x
更新日期:1981-10-01 00:00:00
abstract::1. Dogs, anaesthetized with chloralose and urethane, were subjected to a 25 min occlusion of the left anterior descending coronary artery. This resulted in ventricular ectopic activity, a reduction in baroreflex sensitivity (BRS, measured following the intravenous administration of phenylephrine), elevations in the ep...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704445
更新日期:2002-01-01 00:00:00
abstract::Cyclo-oxygenase (COX) inhibitors potentiate opioid inhibition of GABAergic synaptic transmission in rat periaqueductal grey (PAG) (Vaughan et al., 1997). In the present study, the relative contribution of cyclo-oxygenase-1 (COX-1) and COX-2 inhibition to this phenomenon was examined by use of whole-cell patch clamp re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701818
更新日期:1998-04-01 00:00:00
abstract::1. The present study was designed to evaluate the nature of intervening agents in L-DOPA- and dopamine-induced neurotoxicity in Neuro-2A cells. 2. In the absence of cells and in conditions of light protection, at 37 degrees C, L-DOPA or dopamine (1 mM) in culture medium degraded spontaneously in a time-dependent manne...
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更新日期:2002-12-01 00:00:00
abstract::1. The alpha 2-adrenoceptor binding sites of rabbit spleen and rat kidney, labelled with [3H]-rauwolscine, were characterized using a range of subtype selective ligands. 2. In rabbit spleen, the alpha-2-adrenoceptor binding sites displayed high affinity for oxymetazoline and WB 4101 and low affinity for prazosin and c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12968.x
更新日期:1990-03-01 00:00:00
abstract::1 A study was made of desensitization in chronically denervated and in normally innervated mouse soleus muscles. 2 Very high concentrations of acetylcholine produced small contractions of the innervated muscles; these were reduced in size when the addition was repeated 1 min after wash-out. 3 Desensitization in innerv...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07620.x
更新日期:1975-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Insulin stimulates the transport of glucose in target tissues by triggering the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Resistance to insulin, the major abnormality in type 2 diabetes, results in a decreased GLUT4 translocation efficiency. Thus, special attention is...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12845
更新日期:2014-12-01 00:00:00
abstract::1. A biliary fistula was prepared in twelve sheep.2. Each animal was given 2 ml. of (14)C-carbon tetrachloride (specific activity 15 mc/m-mole) and bile collected at 2, 4, 24 and 48 hr.3. Specific activity was measured by liquid scintillation counting before and after each specimen had been heated to 75 degrees C for ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09502.x
更新日期:1969-06-01 00:00:00
abstract::1. The effect of adenosine triphosphate (ATP) and its stable analogues, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, on the efferent function of capsaicin-sensitive non-adrenergic, non-cholinergic (NANC) nerves was tested in guinea-pig isolated atria. 2. Transmural nerve stimulation of atria isolated from ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09011.x
更新日期:1992-03-01 00:00:00
abstract::1. Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with th...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0701146
更新日期:1997-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Hydrogen sulphide (H(2)S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H(2)S in blood and tissues. EXPERIMENTAL APPROACH:Concentrations of reactive...
journal_title:British journal of pharmacology
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更新日期:2010-06-01 00:00:00
abstract::1 The venom of the green mamba, Dendroaspis angusticeps, was tested for effects on neuromuscular transmission and skeletal muscle contractility in isolated phrenic nerve-hemidiaphragm preparations of the rat and mouse, chick biventer cervicis muscle preparations and in aneural cultures of embryonic chick skeletal musc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb08667.x
更新日期:1979-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Macropinocytosis is involved in many pathologies, including cardiovascular disorders, cancer, allergic diseases, viral and bacterial infections. Unfortunately, the currently available pharmacological inhibitors of macropinocytosis interrupt other endocytic processes and have non-specific endocyto...
journal_title:British journal of pharmacology
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更新日期:2018-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:There is increasing evidence that potassium channels are involved in the cardiovascular dysfunction of sepsis. This evidence was obtained after the systemic inflammation, cardiovascular dysfunction and organ damage had developed. Here we have studied the consequences of early interference with po...
journal_title:British journal of pharmacology
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更新日期:2011-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The effects of bergamot essential oil (BEO; Citrus bergamia, Risso) on excitotoxic neuronal damage was investigated in vitro. EXPERIMENTAL APPROACH:The study was performed in human SH-SY5Y neuroblastoma cells exposed to N-methyl-D-aspartate (NMDA). Cell viability was measured by dye exclusion. R...
journal_title:British journal of pharmacology
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更新日期:2007-06-01 00:00:00
abstract::1. In mouse pancreatic beta-cells the regulation of the diazoxide-sensitivity of the adenosine 5'-triphosphate-dependent K+ channel (K-ATP-channel) was examined by use of the patch-clamp technique. 2. In intact beta-cells incubated at 37 degrees C in the presence of 3 mM D-glucose, diazoxide did not affect the single ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14467.x
更新日期:1992-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Advanced glycation endproducts (AGE) have been implicated in the pathogenesis of diabetic complications, including diabetic cardiovascular dysfunctions. 3-benzyloxycarbonylmethyl-4-methyl-thiazol-3-ium bromide (C36), a novel AGE breaker, was investigated for its beneficial effects on the cardiova...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0707533
更新日期:2007-12-01 00:00:00
abstract::1. N-formyl peptides (e.g. fMLP; N-formyl-L-methionyl-L-leucyl-phenylalanine) are potent mediators for inflammatory reactions. We report functional expression in Xenopus oocytes of human fMLP-R98 cDNA, without co-expression of the promiscuous G-protein subunit, Galpha-16. 2. Stimulation of voltage-clamped oocytes (-70...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704592
更新日期:2002-03-01 00:00:00
abstract::1. Morphine-like analgesic drugs caused depression of twitches of the isolated guinea-pig ileum in response to transmural electrical stimulation. The drugs tested were the narcotic analgesics codeine, diamorphine, fentanyl, morphine, morphine-N-oxide, normorphine, oxymorphone, pethidine, phenazocine and phenoperidine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb10580.x
更新日期:1969-10-01 00:00:00
abstract::1. To investigate the role of long-term stimulation of nicotinic acetylcholine receptors (AChRs) on the regulation of membrane potential, non-contracting C2C12 myotubes were stimulated for 1-4 days with carbachol (10 microM) and membrane potentials were measured by the intracellular microelectrode technique after wash...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14758.x
更新日期:1994-02-01 00:00:00