Agonists and protein kinase C-activation induce phosphorylation and internalization of FFA1 receptors.


:FFA1 (previously known as GPR40) is a free fatty acid receptor involved in the regulation of inflammatory processes and insulin secretion. The cellular actions resulting from FFA1 activation have received considerable attention. However, little is known on the regulation of the receptor function. In the present work, using cells transfected with this receptor, docosahexaenoic acid and α-linolenic acid increased intracellular calcium concentration and ERK 1/2 phosphorylation. It was also observed that FFA1 is a phosphoprotein whose phosphorylation state was increased (2- to 3-fold) by agonists (i.e., free fatty acids) and also by phorbol myristate acetate. Agonist- and phorbol ester-mediated FFA1 phosphorylation was markedly reduced by inhibitors of protein kinase C. Receptor stimulation by free fatty acids and protein kinase C activation also induced receptor internalization as evidenced by confocal microscopy. In summary, our data show that FFA1 is a phosphoprotein whose phosphorylation state is modulated by agonists and protein kinase C activation; such covalent modification is associated with receptor internalization.


Eur J Pharmacol


Sosa-Alvarado C,Hernández-Méndez A,Romero-Ávila MT,Sánchez-Reyes OB,Takei Y,Tsujimoto G,Hirasawa A,García-Sáinz JA




Has Abstract


2015-12-05 00:00:00












  • The beneficial in vitro effects of lovastatin and chelerythrine on relaxatory response to acetylcholine in the perfused mesentric bed isolated from diabetic rats.

    abstract::Diabetes mellitus is associated with an increased risk of cardiovascular disease. Endothelial dysfunction (i.e. decreased endothelium-dependent vasorelaxation) plays a key role in the pathogenesis of diabetic vascular disease. The present study was undertaken to determine whether diabetes induced by streptozotocin alt...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Fatehi-Hassanabad Z,Imen-Shahidi M,Fatehi M,Farrokhfall K,Parsaeei H

    更新日期:2006-03-27 00:00:00

  • Effects of branched-chain amino acids on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes.

    abstract::We investigated the effects of branched-chain amino acids on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. Of the branched-chain amino acids, only leucine (10(-5)-10(-3) M) induced hepatocyte DNA synthesis and proliferation in a time- and dose-dependent manner. The addition of valine or...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Kimura M,Ogihara M

    更新日期:2005-03-14 00:00:00

  • Lack of effect of 6-hydroxydopamine pretreatment on depolarization-induced release of ATP fron rat brain synaptosomes.

    abstract::Pretreatment of rats with intraventricular 6-hydroxydopamine produced considerable destruction of noradrenergic and dopaminergic nerve terminals as indicated by depletions in synaptosomal catecholamine contents. However, 6-hydroxydopamine pretreatment did not result in diminished release of ATP during depolarization o...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Potter PE,White TD

    更新日期:1982-05-07 00:00:00

  • Vincamine and vincanol are potent blockers of voltage-gated Na+ channels.

    abstract::The effects of three vinca derivatives on [3H]batrachotoxin binding in rat cortical synaptosomes, on the inhibition of whole-cell Na+ currents evoked in voltage-clamped cortical neurones of the rat, on the protection against veratridine-induced cell death in cortical cultures and on the maximal electroshock-induced se...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Erdo SA,Molnár P,Lakics V,Bence JZ,Tömösközi Z

    更新日期:1996-10-24 00:00:00

  • Effect of cyclosporin A on morphine-induced place conditioning in mice: involvement of nitric oxide.

    abstract::Cyclosporin A is shown to attenuate antinociceptive effects of morphine, development and expression of morphine-induced tolerance and dependency via nitric oxide (NO) pathway. In the present study, the effect of systemic cyclosporin A on morphine-induced conditioned place preference (CPP) and the probable involvement ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Motiei Langroudi R,Khoshnoodi MA,Abadi NY,Tahsili Fahadan P,Ghahremani MH,Dehpour AR

    更新日期:2005-01-10 00:00:00

  • The loss of susceptibility to apoptosis in exudated tissue neutrophils is associated with their nuclear factor-kappa B activation.

    abstract::Tissue neutrophils, human salivary neutrophils donated from healthy subjects and synovial fluid neutrophils collected from patients with rheumatoid arthritis were compared with circulating blood neutrophils. Concomitant treatment of circulating blood neutrophils with tumor necrosis factor-alpha (TNF-alpha) and cyclohe...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Hotta K,Niwa M,Hara A,Ohno T,Wang X,Matsuno H,Kozawa O,Ito H,Kato K,Otsuka T,Matsui N,Uematsu T

    更新日期:2001-12-14 00:00:00

  • Electrophysiological effect and the gating mechanism of astragaloside IV on L-type Ca(2+) channels of guinea-pig ventricular myocytes.

    abstract::Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalus membranaceus. This study is aimed to investigate AS-IV׳s effects on Ca(2+) channel activity of single cardiomyocytes and single Ca(2+) channels. Whole-cell Ca(2+) currents in freshly dissociated cardiomyocytes were measured using the whole-ce...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Zhao M,Shao D,Yu L,Sun X,Wang Y,Hu H,Feng R,Gao Q,Guo F,Hao L

    更新日期:2015-08-05 00:00:00

  • Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity.

    abstract::The inhibitory action of bicyclic isoxazole gamma-aminobutyric acid (GABA) analogues and their 4,4-diphenyl-3-butenyl (DPB) substituted derivatives has been investigated in cortical neurones and astrocytes as well as in human embryonic kidney (HEK 293) cells transiently expressing either mouse GABA transporter-1 (GAT-...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Bolvig T,Larsson OM,Pickering DS,Nelson N,Falch E,Krogsgaard-Larsen P,Schousboe A

    更新日期:1999-06-30 00:00:00

  • Apoptosis, 5-fluorouracil sensitivity and expression of apoptotic proteins in a human ectocervical cell carcinogenesis model using different media.

    abstract::Apoptosis has received widespread attention for its essential roles in biology, medicine and cancer. We previously found that normal, human papillomavirus (HPV) 16-immortalized and their transformed endocervical cells were increasingly resistant to apoptosis induced by a cancer therapeutic drug. Here, analogously, ano...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Mo B,Pater A

    更新日期:2003-04-25 00:00:00

  • Behavioral sensitization to the discriminative stimulus effects of methamphetamine in rats.

    abstract::Sensitization to the discriminative stimulus effects of psychostimulants is not fully understood. Therefore, the present study was designed to investigate the development of sensitization to the discriminative stimulus of methamphetamine in rats. A dose-response curve for methamphetamine and a generalization test for ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Suzuki T,Fukuoka Y,Mori T,Miyatake M,Narita M

    更新日期:2004-09-13 00:00:00

  • Comparison of pharmacological activities of Neuropeptide FF1 and Neuropeptide FF2 receptor agonists.

    abstract::The pharmacological effects of Neuropeptide FF (NPFF) analogs exhibiting different selectivities towards Neuropeptide FF1 (NPFF1) and Neuropeptide FF2 (NPFF2) receptors were investigated after supraspinal administration in mice. Injected into the third ventricle, VPNLPQRF-NH2, which is selective for Neuropeptide FF1 r...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Quelven I,Roussin A,Zajac JM

    更新日期:2005-01-31 00:00:00

  • Hsp70 promotes synaptic transmission in brain slices damaged by contact with blood clot.

    abstract::Neurotrophic and neuroprotective properties of Hsp70 were studied in olfactory cortex slices of hypertensive rats under normal conditions and under influence of autologous blood (blood clot). Under normal conditions, synaptic response in slices depended on Hsp70 amount in medium. Incubation of slices with Hsp70 showed...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Mokrushin AA,Pavlinova LI

    更新日期:2012-02-29 00:00:00

  • Angiotensin-converting enzyme: presence of high activity in choroid plexus of mammalian brain.

    abstract::The activity of angiotensin-converting enzyme in rat choroid plexus was higher than that of any other organ, being 6--7 times higher than that in lung and more than 50 times higher than in any other region of brain. Rabbit choroid plexus also had high activity of enzyme while that of human choroid plexus was relativel...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Arregui A,Iversen LL

    更新日期:1978-11-01 00:00:00

  • Effects of the putative lithium mimetic ebselen on pilocarpine-induced neural activity.

    abstract::Lithium, commonly used to treat bipolar disorder, potentiates the ability of the muscarinic agonist pilocarpine to induce seizures in rodents. As this potentiation by lithium is reversed by the administration of myo-inositol, the potentiation may be mediated by inhibition of inositol monophosphatase (IMPase), a known ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Singh N,Serres F,Toker L,Sade Y,Blackburn V,Batra AS,Saiardi A,Agam G,Belmaker RH,Sharp T,Vasudevan SR,Churchill GC

    更新日期:2020-09-15 00:00:00

  • Comparison of the antiplatelet effect of YM337 and abciximab in rhesus monkeys.

    abstract::We directly compared the effects of YM337, the Fab fragment of the humanized monoclonal antibody C4G1, on platelet aggregation and template bleeding time with those of abciximab, the Fab fragment of the human/murine chimeric monoclonal antibody 7E3, in rhesus monkeys. The duration of inhibition of platelet aggregation...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Suzuki K,Sakai Y,Hisamichi N,Taniuchi Y,Sato K,Terazaki C,Kaku S,Kawasaki T,Yano S,Inagaki O,Masuho Y

    更新日期:1997-10-08 00:00:00

  • Role of spinal kappa opioid receptors in the blockade of the development of antinociceptive tolerance to morphine.

    abstract::The site of action of the kappa opioid receptor agonist, U-50,488H in suppressing the development of tolerance to morphine antinociception was examined by local application, either intrathecal (i.t., spinal) or intracerebroventricular (i.c.v., supraspinal) in mice. Mice given morphine s.c., i.c.v. or i.t. daily develo...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Takahashi M,Senda T,Kaneto H

    更新日期:1991-08-06 00:00:00

  • Augmented thromboxane generation by mesenteric arteries from pancreatectomized diabetic dogs is coincident with the vascular tone enhancement evoked by Na arachidonate and prostacyclin.

    abstract::We studied the relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA) and the prostaglandins (PGs) in mesenteric arteries isolated from sham-operated and totally pancreatectomized dogs. PGE2 and PGF2 alpha produced a similar dose-dependent relaxation of mesenteric art...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Sterin-Borda L,Franchi AM,Borda ES,Del Castillo E,Gimeno MF,Gimeno AL

    更新日期:1984-08-17 00:00:00

  • MPP+ inhibits mGluR1/5-mediated long-term depression in mouse hippocampus by calpain activation.

    abstract::Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of n...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Li J,Chen H,Wu S,Cheng Y,Li Q,Wang J,Zhu G

    更新日期:2017-01-15 00:00:00

  • The antiarrhythmic action of amitriptyline on arrhythmias associated with myocardial infarction in dogs.

    abstract::The antiarrhythmic activity of amitriptyline, a tricyclic antidepressant, was evaluated in anesthetized dogs 24 h after coronary occlusion, during the period of spontaneous ventricular arrhythmias. In all experiments amitriptyline was administered i.v. in incremental doses of 0.3 mg/kg at 1 min intervals until a conve...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Wilkerson RD,Sanders PW

    更新日期:1978-10-01 00:00:00

  • Effects of antidepressant drugs on different receptors in the brain.

    abstract::Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors. The tricyclic antidepressants more or less potently inhibited the binding to rat brain preparations of several different radiolabelled ligands [3H]WB4101, [...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Hall H,Ogren SO

    更新日期:1981-03-26 00:00:00

  • 2-Arachidonylglycerol, an endogenous cannabinoid, inhibits tumor necrosis factor-alpha production in murine macrophages, and in mice.

    abstract::2-Arachidonylglycerol (2-AG) inhibits the production in vitro of tumor necrosis factor-alpha (TNF-alpha) by mouse macrophages, as well as in mice. It has no effect on the production of nitric oxide (NO). The effect on TNF-alpha is enhanced when 2-AG is administered together with 2-linoleylglycerol (2-Lino-G) and 2-pal...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Gallily R,Breuer A,Mechoulam R

    更新日期:2000-10-06 00:00:00

  • Telenzepine enantiomers block muscarinic M1-receptors with opposite kinetics.

    abstract::Stimulation of muscarinic M1-receptors in isolated rabbit vas deferens by McN-A-343 inhibited electrically induced twitch contractions susceptible to competitive blockade by (+)-, (+/-), (-)-telenzepine and pirenzepine (pA2 = 9.12, 8.86, 6.98 and 7.79, respectively). The inhibition of twitch contractions by 10(-6) M M...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Eltze M

    更新日期:1990-05-03 00:00:00

  • Effect of nifedipine on cyclosporine A-induced nephrotoxicity, urinary endothelin excretion and renal endothelin receptor number.

    abstract::The aim of the present study was to determine the effect of a calcium channel blocker on renal function, urinary endothelin excretion and endothelin receptor number in rats. Administration of cyclosporine resulted in a significant impairment of renal function when measured by either [14C]inulin or 24 h creatinine clea...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Brooks DP,Ohlstein EH,Contino LC,Storer B,Pullen M,Caltabiano M,Nambi P

    更新日期:1991-02-26 00:00:00

  • A comparison of the stimulant activities of oxotremorine analogues on the frog rectus abdominis and the guinea pig ileum.

    abstract::A series of tertiary amines structurally related to the potent muscarinic agent oxotremorine showed weak stimulant activity on the frog rectus abdominis preparation. The corresponding quaternary ammonium salts were more effective stimulants, the most potent being half as active as carbachol. The effects appeared to be...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Ringdahl B

    更新日期:1984-03-23 00:00:00

  • SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons.

    abstract::SCH-23390, a selective D-1 dopamine antagonist, was found to antagonize the locomotor stimulation induced by LY-171555, an action similar to that for haloperidol in control animals. However, this action of SCH-23390 was prevented in rats treated with 6-hydroxydopamine (6-OHDA) or with reserpine plus alpha-methyl-tyros...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Breese GR,Mueller RA

    更新日期:1985-07-11 00:00:00

  • Tolterodine--a new bladder-selective antimuscarinic agent.

    abstract::Tolterodine is a new muscarinic receptor antagonist intended for the treatment of urinary urge incontinence and other symptoms related to an overactive bladder. The aim of the present study was to compare the antimuscarinic properties of tolterodine with those of oxybutynin, in vitro and in vivo. Tolterodine effective...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Nilvebrant L,Andersson KE,Gillberg PG,Stahl M,Sparf B

    更新日期:1997-05-30 00:00:00

  • Molecular pharmacology of LR-B/081, a new non-peptide angiotensin AT1 receptor antagonist.

    abstract::This report describes the molecular pharmacological properties 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-thiophenecarboxilate), a novel non-peptide angiotensin II receptor antagonist. This compound potently displaced [3H]angiote...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Renzetti AR,Criscuoli M,Salimbeni A,Subissi A

    更新日期:1995-07-18 00:00:00

  • Chelerythrine and bisindolylmaleimide I prolong cardiac action potentials by protein kinase C-independent mechanism.

    abstract::Effects of chelerythrine and bisindolylmaleimide I on action potential duration and on voltage-activated K(+) and Ca(2+) currents in rat ventricular myocytes were studied using perforated patch-clamp technique. The action potentials were markedly prolonged after application of 20 microM chelerythrine or 100 nM bisindo...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Voutilainen-Myllylä S,Tavi P,Weckström M

    更新日期:2003-04-11 00:00:00

  • Effect of azelastine on platelet-activating factor and antigen-induced pleurisy in rats.

    abstract::The interference of azelastine with pleurisy induced by antigen was investigated in actively sensitized rats. The antigenic challenge (ovalbumin, 12 micrograms/cavity) caused early plasma leakage, which peaked within 4 h, accompanied by intense neutrophil infiltration. Pleural exudate decayed 24 h after antigen provoc...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Lima MC,Martins MA,Perez SA,Silva PM,Cordeiro RS,Vargaftig BB

    更新日期:1991-05-17 00:00:00

  • The role of endothelium-derived hyperpolarizing factor and cyclooxygenase pathways in the inhibitory serotonergic response to the pressor effect elicited by sympathetic stimulation in chronic sarpogrelate treated rats.

    abstract::We have demonstrated that the antagonism of 5-HT2 receptors produces an enhancement of serotonergic sympathoinhibitory effect by 5-HT1D and 5-HT7 activation. The aim of this work was to determine mechanisms involved in the 5-hydroxytriptaminergic inhibitory action on the pressor responses elicited by sympathostimulati...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: García-Pedraza JÁ,García M,Martín ML,San Román L,Morán A

    更新日期:2014-05-15 00:00:00