The effects of anandamide transport inhibitor AM404 on voltage-dependent calcium channels

Alptekin, Alp; Galadari, S.; Shuba, Yaroslav; Petroianu, Georg; Öz, Murat

doi:10.1016/j.ejphar.2010.02.013

Cited by 17 publications

(6 citation statements)

References 31 publications

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“…For instance, ANA is transported to the interior of the cell via putative transporters. Despite the apparent lack of molecular evidence for a carrier-mediated transport of ANA across the membrane (ANA membrane transporter, AMT) and the debate on its existence, particularly in view of the fact that the lipophilicity of ANA would allow it to cross the plasma membrane by passive diffusion, experimental evidence suggest indeed, the neurobiological role of the putative AMT [85,86].…”

Section: Biosynthesis and Degradation Of The Endocannabinoidsmentioning

confidence: 97%

The Emerging Role of the Endocannabinoid System in the Sleep-Wake Cycle Modulation

Murillo-Rodrı́guez¹,

Poot-Aké²,

Arias-Carrión³

et al. 2011

CNSAMC

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The endocannabinoid system comprises amides, esters and ethers of long chain polyunsaturated fatty acids. Narachidonoylethanolamide (anandamide; ANA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids (endocannabinoids) ligands for the cannabinoid family of G-protein-coupled receptors named CB1 and CB2. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and behave as retrograde signaling messengers, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters systems. The two principal enzymes that are responsible for the metabolism of ANA and 2-AG are fatty acid amide hydrolase and monoacylglycerol lipase, respectively. Pharmacological experiments have shown that the administration of endocannabinoids induce cannabimimetic effects, including sleep promotion. This review will focus on some of the current evidence of the pharmacological potential of the endocannabinoid system on sleep modulation.

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Section: Biosynthesis and Degradation Of The Endocannabinoidsmentioning

confidence: 97%

The Emerging Role of the Endocannabinoid System in the Sleep-Wake Cycle Modulation

Murillo-Rodrı́guez¹,

Poot-Aké²,

Arias-Carrión³

et al. 2011

CNSAMC

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“…We propose two alternative scenarios to account for such effects of "transport inhibitors": 1) that in addition to inhibiting FABPs, transport inhibitors target a putative trans-synaptic protein that mediates retrograde endocannabinoid transport and/or 2) that these compounds engage off-target receptor systems. With regard to the latter, it is known that AM404 activates transient receptor potential vanilloid receptor 1 (52), sodium channels (53,54), and calcium channels (55), and some of its physiological effects likely stem from such off-target interactions (56). VDM11 induces hypomotility in rats (57) and inhibits FAAH (7,30).…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid-binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors

Kaczocha

Vivieca

Sun

et al. 2012

Journal of Biological Chemistry

163

197

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Background: Transport inhibitors modulate endocannabinoid signaling by inhibiting their uptake through unknown mechanisms. Results: Effects of transport inhibitors upon endocannabinoid uptake and intracellular trafficking were lost in the absence of fatty acid-binding proteins. Conclusion: Fatty acid-binding proteins are physiological targets of transport inhibitors. Significance: These findings identify drug targets for modulating endocannabinoid signaling.

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“…We have previously reported that major NAE species, including AEA, produced during ischaemia have significant effects on the amplitudes and kinetics of APs and accompanying ionic currents that could account for the negative ionotropic actions of these compounds on ventricular myocytes (Voitychuk et al, 2012). For example, functions of voltagegated Ca 2+ (Oz et al, 2000); (Oz et al, 2004;Alptekin et al, 2010;Voitychuk et al, 2012) and Na + (Gulaya et al, 1993;Voitychuk et al, 2012) channels are modulated by NAEs. In the concentration range used in our study, AEA inhibited the function of various cardiac ion channels in cannabinoid receptor-independent manner.…”

Section: Figurementioning

confidence: 99%

Effects of the endogenous cannabinoid anandamide on voltage‐dependent sodium and calcium channels in rat ventricular myocytes

Kury

Voitychuk

Yang

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEThe endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. EXPERIMENTAL APPROACHWhole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. KEY RESULTSIn the presence of 1-10 μM AEA, suppression of both Na + and L-type Ca 2+ channels was observed. Inhibition of Na + channels was voltage and Pertussis toxin (PTX) -independent. Radioligand-binding studies indicated that specific binding of [ 3 H] batrachotoxin (BTX) to ventricular muscle membranes was also inhibited significantly by 10 μM metAEA, a non-metabolized AEA analogue, with a marked decrease in Bmax values but no change in Kd. Further studies on L-type Ca 2+ channels indicated that AEA potently inhibited these channels (IC50 0.1 μM) in a voltage-and PTX-independent manner. AEA inhibited maximal amplitudes without affecting the kinetics of Ba 2+ currents. MetAEA also inhibited Na + and L-type Ca 2+ currents. Radioligand studies indicated that specific binding of [ CONCLUSION AND IMPLICATIONSResults indicate that AEA inhibited the function of voltage-dependent Na + and L-type Ca 2+ channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation.

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The effects of anandamide transport inhibitor AM404 on voltage-dependent calcium channels

Cited by 17 publications

References 31 publications

The Emerging Role of the Endocannabinoid System in the Sleep-Wake Cycle Modulation

The Emerging Role of the Endocannabinoid System in the Sleep-Wake Cycle Modulation

Fatty Acid-binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors

Effects of the endogenous cannabinoid anandamide on voltage‐dependent sodium and calcium channels in rat ventricular myocytes

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