Abstract:
:1. In this study we examined the effects of cortistatin, a putative endogenous ligand for somatostatin (SRIF) receptors, on the membrane properties of rat locus coeruleus (LC) neurones in vitro, by use of intracellular and whole cell patch clamp recording. We have compared the actions of cortistatin with those of SRIF and the SRIF analogue D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP). 2. When LC neurones were voltage clamped to -60 mV, application of cortistatin caused an outward current in all cells examined (n = 44), with a pEC50 of 6.62. SRIF also caused an outward current in all cells examined (n = 43), with a pEC50 of 6.93. 3. The outward currents caused by cortistatin in 2.5 mM extracellular K+ reversed polarity at -106 mV, very close to the predicted K+ reversal potential of -105 mV. Increasing extracellular K+ to 10.5 mM resulted in a shift of the reversal potential of +38 mV, a shift consistent with a K+ conductance. The conductance activated by cortistatin showed mild inward rectification. 4. Continuous application of a high concentration of SRIF (1 microM) resulted in a decrease of the outward current to a steady level of 49% of the maximum response, with a t1/2 of 131 s. Application of a high concentration of cortistatin (3 microM) during the desensitized portion of the SRIF response did not result in any further outward current. Continuous application of a high concentration of cortistatin (10 microM) resulted in a decrease of the outward current to a steady level of 42% of the maximum response with a t1/2 of 114 s. Application of a high concentration of SRIF (3 microM) during the desensitized portion of the cortistatin response produced only a small outward current. 5. Continuous application of cortistatin (3 microM) also resulted in a decrease of the outward current (by 43%, t1/2 of 136 s) and application of a high concentration of CTOP (10 microM) during the desensitized portion of the cortistatin response did not produce any outward current. Continuous application of a high concentration of CTOP (10 microM) resulted in a decrease of the outward current to a steady level of 70% of the maximum response with a t1/2 of 143 s. Application of a high concentration of cortistatin (3 microM) during the desensitized portion of the CTOP response did not result in any further outward current. 6. The actions of cortistatin (300 nM-10 microM) were not affected by the opioid antagonist naloxone (10 microM). Application of met-enkephalin during the desensitized portion of the response to a high concentration of cortistatin (3 microM) produced an outward current similar to that produced by metenkephalin application alone. 7. Thus cortistatin efficaciously activates an inwardly rectifying K+ conductance in LC neurones. These actions appear to be mediated by a population of SRIF receptors, at which CTOP is also an agonist. Cortistatin does not appear to be a ligand for mu-opioid receptors in rat LC neurons.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Connor M,Ingram SL,Christie MJdoi
10.1038/sj.bjp.0701541subject
Has Abstractpub_date
1997-12-01 00:00:00pages
1567-72issue
8eissn
0007-1188issn
1476-5381journal_volume
122pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Cytochrome P450 (CYP, P450) 3A4 is involved in the metabolism of 50% of drugs and its catalytic activity in vivo is not explained only by hepatic expression levels. We previously demonstrated that UDP-glucuronosyltransferase (UGT) 2B7 suppressed CYP3A4 activity through an interaction. In the pres...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14900
更新日期:2020-03-01 00:00:00
abstract::GPCRs can interact with each other to form homomers or heteromers. Homomers involve interactions with the same receptor type while heteromers involve interactions between two different GPCRs. These receptor-receptor interactions modulate not only the binding but also the signalling and trafficking properties of indivi...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12798
更新日期:2014-09-01 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
abstract::Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMD...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706086
更新日期:2005-02-01 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::1. Male rats treated with guanethidine 25 mg/kg daily for eight weeks had no demonstrable ejaculatory function immediately after cessation of treatment. Four weeks later, ejaculatory function had returned in two-thirds of the males, and after eight weeks, all males were able to deposit sperm in the vagina. However, fe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08219.x
更新日期:1973-05-01 00:00:00
abstract::1. Several cations (Ba2+, Cd2+, Co2+, Cu2+, Mn2+, Ni2+, Zn2+ and La3+, all as chloride salts, 1-1000 microM) were tested in the guinea-pig urinary bladder for their ability to: (i) modify contractile responses to electrical field stimulation (EFS), ATP, alpha,beta-methylene ATP (alpha,beta-meATP), carbachol (CCh), and...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb17186.x
更新日期:1995-02-01 00:00:00
abstract::1. A method is presented which enables the dissociation constant (KI) of a competitive, pseudo-irreversible or non-competitive antagonist-receptor complex to be estimated without knowledge of agonist concentrations. 2. The technique has been tested using sets of concentration-response data which simulated these variou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14047.x
更新日期:1994-01-01 00:00:00
abstract::1. The effects of 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo-cyclic GMP) on phenylephrine-induced contractions and phosphatidylinositol (PI) hydrolysis were investigated in rat isolated caudal artery. The effects of the nucleotide were compared to those of felodipine, a dihydropyridine Ca2+ channel antagonis...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16394.x
更新日期:1995-09-01 00:00:00
abstract::1 Embryonic sensory neurones of the chick grown in dissociated cell culture respond to application of low concentrations of gamma-aminobutyric acid (GABA) with a change in resting membrane resistance (R(in)) and/or a change in action potential duration (APD) (Dunlap & Fischbach, 1978; Choi & Fischbach, 1981). Intracel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10467.x
更新日期:1981-11-01 00:00:00
abstract::1. To clarify the role of the first thrombin receptor/protease-activated receptor (PAR)-1 in an inflammatory process, we tested and characterized the effect of intraplantar (i.pl.) administration of the highly specific PAR-1 agonist TFLLR-NH2 in rat hindpaw. 2. TFLLR-NH2 administered i.pl. at 0.01-0.03 micromol per pa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702513
更新日期:1999-04-01 00:00:00
abstract::1. Moclobemide (MB) is an antidepressant drug that selectively and reversibly inhibits monoamine oxidase-A. Recent studies have revealed that antidepressant drugs possess the characters of potent growth-promoting factors for the development of neurogenesis and improve the survival rate of serotonin (5-hydroxytrytamine...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706766
更新日期:2006-07-01 00:00:00
abstract::Oxidized ATP (oATP) is a Schiff-base-forming reagent that has been used for some years as an antagonist at the P2X7 receptor (P2X7R). Preincubation of mononuclear phagocytes with this inhibitor leads to attenuation of several proinflammatory responses triggered by extracellular ATP as well as a few non-nucleotide agon...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章,评审
doi:10.1038/sj.bjp.0705469
更新日期:2003-10-01 00:00:00
abstract::1. We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702132
更新日期:1998-10-01 00:00:00
abstract::1. In pithed rats, preganglionic vagal nerve stimulation (at 5 Hz) elicited a bradycardia. This bradycardia was potentiated by the angiotensin converting enzyme inhibitor, captopril (1 mg kg-1, i.v.) by about 40%. Subsequent angiotensin II infusion (0.03 micrograms kg-1 min-1) reversed this effect. A similar facilitat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13807.x
更新日期:1993-09-01 00:00:00
abstract::Synaptic transmission in the isolated olfactory cortex slice from the rat was monitored by recording the surface field potentials evoked on lateral olfactory tract (LOT) stimulation. Catechol (approximately 0.05 to 2 mM) caused a concentration-dependent, partially reversible increase in the amplitudes of all field pot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10221.x
更新日期:1986-06-01 00:00:00
abstract::1. The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG-monomethyl-L-arginine (L-NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine. 2. Portal hypertension was induced by partial portal vein liga...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14233.x
更新日期:1992-01-01 00:00:00
abstract::1 The possible involvement of N-methyl-D-aspartate (NMDA)-receptors in epileptiform synaptic activity in the kainic acid (KA) lesioned hippocampus was investigated. In this chronic model of epilepsy there is a loss of both the early and the late components of synaptic inhibition as well as changes in the membrane prop...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11280.x
更新日期:1987-08-01 00:00:00
abstract::Adenosine 5'-triphosphate (ATP) and adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP) both contracted the guinea-pig urinary bladder, but the response to AMP-PCP was much greater. We synthesized the enantiomer of AMP-PCP, L-adenylyl 5'-(beta, gamma-methylene)-diphosphonate (L-AMP-PCP), and tested it on the g...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16453.x
更新日期:1984-05-01 00:00:00
abstract::The aim of this study was to characterize the angiotensin II receptors in isolated uterine arteries from non pregnant and pregnant rats, since it has been reported from binding studies that ovine uterine arteries contain AT2 receptors. Uterine arterial segments were obtained from virgin, non-pregnant and late pregnant...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702210
更新日期:1998-12-01 00:00:00
abstract::1. The ability of a range of substituted imidazole compounds to inhibit mouse cerebellar neuronal nitric oxide synthase (nNOS), bovine aortic endothelial NOS (eNOS) and inducible NOS (iNOS) from lungs of endotoxin-pretreated rats was investigated. In each case the substrate (L-arginine) concentration employed was 120 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16003.x
更新日期:1996-09-01 00:00:00
abstract::An approximate eight fold desensitization of the circular coat of the distal rabbit colon to adenosine 5'-triphosphate (ATP) and adenosine could be achieved by repeatedly exposing the organ to relatively low concentrations (10-100 microM) of these compounds. The desensitization was specific and reversible after prolon...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08788.x
更新日期:1982-02-01 00:00:00
abstract::N-methyl-d-aspartate (NMDA) receptors have been demonstrated to be a pivotal target for ethanol action. The present study examined the actions of acute ethanol exposure on NMDA-induced responses and the acute tolerance to ethanol actions in rat sympathetic preganglionic neurons (SPNs) in vitro and in vivo. NMDA (50 mi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705512
更新日期:2003-11-01 00:00:00
abstract::Vasoactive intestinal peptide (VIP) caused concentration-dependent relaxation in precontracted segments of trachea, hilar bronchus, intrapulmonary bronchus and intrapulmonary artery (IPA) isolated from cat lungs. VIP-induced relaxation responses were abolished by preincubation of tissues with the proteolytic enzyme, a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10766.x
更新日期:1984-06-01 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
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707533
更新日期:2007-12-01 00:00:00
abstract::1. Effects of an orally active non-peptide (BK) B2 receptor antagonist, FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinoli nyl) oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide) on the plasma exudation in rat carrageenin-induced pleurisy were investigated. 2. Plasma exudation in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701194
更新日期:1997-06-01 00:00:00
abstract::1. Ca currents in rat and mouse sensory dorsal root ganglion (DRG) neurones were inhibited by concentrations of (-)-baclofen as low as 1 micron. The proportion of neurones responding to baclofen was low (less than 20%), except in young cultures of neonate rat DRG neurones (3 days in culture), where 86% of the neurones...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11520.x
更新日期:1988-05-01 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:BACKGROUND AND PURPOSE:The aim of the present study was to assess the interaction of nitrergic neurotransmission within the bed nucleus of the stria terminalis (BNST) with local glutamatergic and noradrenergic neurotransmission in the control of cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14447
更新日期:2018-10-01 00:00:00
abstract::1. gamma-Aminobutyric acid (GABA) was applied by the 'concentration clamp' technique to isolated neurones of Aplysia. GABA induced a chloride current (ICl) due to activation of a single class of chloride-channel. 2. The concentration-response curve for the peak ICl gave an apparent dissociation constant of 6.4 X 10(-5...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11718.x
更新日期:1988-11-01 00:00:00