Reviews of Physiology, Biochemistry and Pharmacology Vol. 169 PDF
Preview Reviews of Physiology, Biochemistry and Pharmacology Vol. 169
Reviews of Physiology, Biochemistry and Pharmacology 169 Reviews of Physiology, Biochemistry and Pharmacology More information about this series at http://www.springer.com/series/112 (cid:1) (cid:1) (cid:1) Bernd Nilius Thomas Gudermann Reinhard Jahn (cid:1) (cid:1) Roland Lill Ole H. Petersen Pieter P. de Tombe Editors Reviews of Physiology, Biochemistry and Pharmacology 169 EditorinChief BerndNilius KULeuven Leuven Belgium Editors ThomasGudermann ReinhardJahn Ludwig-Maximilians-Universita¨tMu¨nchen Max-Planck-InstforBiophysical Munich,Germany Chemistry Go¨ttingen RolandLill Germany UniversityofMarburg Marburg OleH.Petersen Germany CardiffSchoolofBiosciences CardiffUniversity PieterP.deTombe Cardiff LoyolaUniversityChicago UnitedKingdom Maywood,Illinois USA ISSN0303-4240 ISSN1617-5786 (electronic) Reviews of Physiology,Biochemistry and Pharmacology ISBN978-3-319-26563-6 ISBN978-3-319-26565-0 (eBook) DOI10.1007/978-3-319-26565-0 SpringerChamHeidelbergNewYorkDordrechtLondon #SpringerInternationalPublishingSwitzerland2015 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilarmethodologynowknownorhereafterdeveloped. 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Printedonacid-freepaper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) Contents Hyperforin:ToBeorNottoBeanActivatorofTRPC(6) ................. 1 KristinaFriedlandandChristianHarteneck ThePiezoMechanosensitiveIonChannels:MaytheForce BewithYou! ................................................................... 25 EricHonore´,JoanaRaquelMartins,DavidPenton, AmandaPatel,andSophieDemolombe ChronobiologyandPharmacologicModulationofthe Renin–Angiotensin–AldosteroneSysteminDogs: WhatHaveWeLearned? ..................................................... 43 JonathanP.MochelandMeindertDanhof v RevPhysiolBiochemPharmacol(2015)169:1–24 DOI:10.1007/112_2015_25 ©SpringerInternationalPublishingSwitzerland2015 Publishedonline:19September2015 Hyperforin: To Be or Not to Be an Activator of TRPC(6) KristinaFriedlandandChristianHarteneck Abstract Meantime, it is well accepted that hyperforin, the chemical instable phloroglucinol derivative of Hypericum perforatum, St. John’s wort, is the pharmacophore of St. John’s wort extracts. With the decline of this scientific discussion,anothercontroversialaspecthasbeenarisen,thequestionregardingthe underlying mechanism leading to the pharmacological profile of the plant extract usedintherapyofdepression.Wewillsummarizethedifferentconceptsdescribed forhyperforin’santidepressiveactivity.Startingwithunspecificprotein-independent mechanisms due to changes in pH, we will summarize data of protein-based concepts beginning with concepts based on involvement of a variety of proteins andwillfinallypresentconceptsbasedonthemodulationofasingleprotein. Keywords Calcium homeostasis (cid:1) Depression (cid:1) Hyperforin (cid:1) Ion channel (cid:1) Protonophore(cid:1)St.John’swort(cid:1)TRPchannel Contents 1 Introduction................................................................................... 2 2 ChemicalStabilityofHyperforinandStableAnalogues................................... 5 3 HyperforinasProtonophore.................................................................. 6 4 HyperforinasInducerofCytochromeP450Enzymes,HyperforinasPregnaneX ReceptorLigand.............................................................................. 9 5 HyperforinasActivatorofIonChannels.................................................... 11 K.Friedland(*) DepartmentofMolecularandClinicalPharmacy,Friedrich-AlexanderUniversityErlangen/ Nuremberg,Cauerstr.4,91058Erlangen,Germany e-mail:[email protected] C.Harteneck(*) InstituteofPharmacologyandToxicologyandInterfacultyCentreforPharmacogenomics andDrugResearch,EberhardKarlsUniversita¨t,Wilhelmstr.56,72074Tu¨bingen,Germany e-mail:[email protected] 2 K.FriedlandandC.Harteneck 6 TheRoleofTRPC6ChannelsforNeuronalEffectsofHyperforin:Depression, Epilepsy,Autism,Ischemia,Cognition,andAlzheimer’sDisease......................... 14 7 Summary...................................................................................... 17 References........................................................................................ 18 1 Introduction St. John’s wort, Hypericum perforatum, is used for centuries to treat mild and moderatedepression(Gastpar2013).Depressionisoneofthemostfrequentdisease worldwide and the most common psychiatric diseases (Duman and Aghajanian 2012;Penninxetal.2013).Approximately1of5womenand1of8mensufferfrom adepressiveepisodeduringtheirlifetime(Mu~nozetal.2010;Murrayetal.2012). Depressionreferstoasetofmentalsymptomssuchaslossofinterestandpleasure, decreased cognition and memory, and disrupted sleeping, eating, ambulation, and sexual activity (Duman and Aghajanian 2012). A large number of clinical trials (Lecrubieretal.2002;Gastparetal.2006;Kasperetal.2010;Singeretal.2011)as wellasarecentCochranemeta-analysis(Lindeetal.2008)confirmtheantidepres- santactivityinpatientsoftheplantanditsextracts.St.John’swortextractscontain several constituents like hyperforin (Fig. 1a), a phloroglucinol derivative, the naphtodianthrone hypericin (Fig. 1b), and some flavonoids such as isoquercitrin, biapigenine,orrutin,whichwerediscussedtorepresenttheantidepressiveprinciple (N€oldner and Sch€otz 2002; Mu¨ller 2003; Butterweck and Schmidt 2007; Paulke etal.2008).Thefirstmoleculeinfocusofrepresentingtheantidepressiveprinciple was hypericin mediating its effect via the inhibition of the monoamine oxidase (Suzukietal.1984).Theseresultscouldnotbevalidated byothergroups arguing foraminorroleofhypericinintheantidepressanteffectsofSt.John’swortextract (BladtandWagner1994;ThiedeandWalper1994;Cott1997).Othermechanisms were investigated such as interaction of hypericin with monoamine receptors (Butterweck et al. 2002; Caccia and Gobbi 2009). However, the concentration gap of hypericin affinities in the micromolar range for binding these receptors and nanomolar plasma concentrations measured in humans after intake of thera- peuticdosesmadeitunlikelytoaccountfortheantidepressiveprinciple(Staffeldt et al. 1994; Kerb et al. 1996; Brockm€oller et al. 1997). Phototoxicity is a feature attracting attention to hypericin (Boiy et al. 2008; Davids et al. 2008), being currentlyunderinvestigationregardingitsantimetastaticandantiangiogenicprop- erties in the treatment of glioblastomas or melanoma (Davids et al. 2008; Barliya et al. 2011; Dror et al. 2013). The flavonoids, biapigenine, hyperoside, and isoquercitrin, showed moderate antidepressive activity in the forced swim test, a behavioral animal model for depression (N€oldner and Sch€otz 2002; Paulke etal.2008)withyetunknownmechanism. Hyperforin (Fig. 1a) was long neglected as the putative antidepressant active constituentofH.perforatumduetoitschemicalinstabilityinresponsetolightand air. Under appropriate storage conditions, 1–5% hyperforin can be found in the Hyperforin:ToBeorNottoBeanActivatorofTRPC(6) 3 A H3C CH3 B OH O OH H3C CH3 OH O O CH3 HO CH3 HO CH3 H3C H3C O CH3 CH3 H3C CH3 OHhypeOricinOH hyperforin C H3C CH3 D H3C CH3 O O O O HO O HO O CH3 H3C CH3 H3C H3C O CH3 HO OH CH3 Hyp9 H3C CH3 aristoforin E O O CH3 O CH3 OH O 1-stearoyl-2-arachidonoyl-sn-glycerol Fig. 1 Structure ofhyperforin (A), hypericin (B), aristoforin (C), Hyp9 (D), and 1-stearoyl-2- arachidonoyl-sn-glycerol(E) St. John’s wort extracts (Chatterjee et al. 1998). The phloroglucinol derivative hyperforinshowedpronouncedeffectsinbehavioralmodelsfordepressioninclud- ingtheforcedswimtest(15mg/kgBW),thelearnedhelplessnesstest(15mgkg/ BW), the elevated plus maze test, or the light/dark test (Chatterjee et al. 1998; Zanoli et al. 2002). Importantly, one clinical trial showed loss of antidepressant properties of a St. John’s wort extract containing 0.5% hyperforin instead of 5% hyperforin (Laakmann et al. 1998). On the biochemical level, several groups showed hyperforin-mediated inhibition of neurotransmitter uptake such as seroto- nin(IC 205nMinwholebrainratsynaptosomes),norepinephrine(IC 102nMin 50 50 rat synaptosomes from the occipital cortex), dopamine (IC 80 nM in synapto- 50 somes isolated from rat striatum), GABA (IC 184 nM in whole brain rat 50 4 K.FriedlandandC.Harteneck synaptosomes),andL-glutamate(IC50143nMinratsynaptosomesisolatedfromrat forebrain) (Chatterjee et al. 1998; Singer et al. 1999; Wonnemann et al. 2000; MarshandDavies2002).Alltransmittersareknownfortheirpotentialroleinthe pathogenesis of depressive disorders (Duman and Aghajanian 2012; Duric and Duman 2013). Increases in extracellular neurotransmitter levels in response to hyperforinwereshowninratsynaptosomes(Chatterjeeetal.2001)andindifferent brain areas using microdialysis (Philippu 2001; Buchholzer et al. 2002; Coskun et al. 2004; Kiewert et al. 2004; Yoshitake et al. 2004) or push–pull analysis (Kaehler et al. 1999). In rat hippocampus, hyperforin (10 mg/kg BW i.p. or 10 μM via the dialysis probe) resulted in increased acetylcholine levels which was completely reverted by local perfusion with calcium-free buffer or in the presence of tetrodotoxin, an inhibitor of voltage-dependent sodium-channels (Buchholzer et al. 2002; Kiewert et al. 2004). Hence, hyperforin-mediated neuro- transmitter release is a calcium-dependent mechanism requiring intact neuronal communication and cell firing (Buchholzer et al. 2002; Kiewert et al. 2004). The impact of hyperforin in increased extracellular accumulation of neurotransmitters like dopamine, norepinephrine, serotonin, and glutamate was measured in the rat locus coeruleus upon application of hyperforin (10 mg/kg BW, i.p. application) (Kaehler et al. 1999). In rat synaptosomes, hyperforin (5 μM) also increased the releaseofseveralneurotransmitterssuchasglutamateorGABA(MarshandDavies 2002).Theseobservationsarguedforthemodulationofsynaptosomalneurotrans- mittertransportbyhyperforin. Pharmacologicalrelevantconcentrationsregardinginhibitionofneurotransmit- ter uptake are achieved in human plasma. The intake of a single dose of 300 mg Hypericumextractcontaining14.8mghyperforinbyhealthyvolunteersresultedin human plasma levels of 150 ng/mL hyperforin (280 nM) (Biber et al. 1998). The applicationoftheclinicaldosage(3(cid:3)300mgSt.John’swortextractperday)given foronedayresultedinhyperforinconcentrationof100ng/mLor180nMinplasma ofhealthyvolunteers(Biberetal.1998).Comparableplasmalevelaswellconcen- trations in brain tissues can be achieved by the application of hyperforin sodium salt. In rats, the application of 300 mg/kg BW Hypericum extract (WS5572, 5% hyperforin) results in plasma concentrations of 370 ng/mL hyperforin (690 nM). Themaximumconcentrationwasdetectedafter3handanestimatedhalf-lifetime of 6 h could be calculated (Biber et al. 1998). The effective dosage used in behavioral test like the forced swim test given as hyperforin sodium salt (15 mg/ kgBW)orasSt.John’swortextract(containing5%hyperforin),resultedinorgan concentrations of 28.8 and 15.8 ng/g (hyperforin per brain tissue) respectively (Kelleretal.2003).Basedonitslipophilicstructure,hyperforinmightaccumulate inthebrainreachinghighernanomolarconcentrationsinthebrainthanfoundinthe plasma. Thediversityofneurotransmitterbeingextracellularlyincreasedinresponseto hyperforin makes it unlikely that hyperforin directly modulates neurotransmitter transport comparable to amitriptyline, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor (Chatterjee et al. 1998; Singer et al. 1999). This is underscored by the fact that the neurotransmitter being modulated by hyperforin is mediated by neurotransmitter transporters of different classes. The
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