Vanilloidireseptori

Seuraa 
Viestejä45973
Liittynyt3.9.2015

Tervehdys listille.

Mulla on pieni toiveenkipinä, että täällä joku saattaisi tietää tarkemmin vanilloidireseptoreista. Haluaisin saada varmennuksen siihen, että olenko ymmärtänyt termit oikein, eli onko vanilloidireseptori synonyymi kapsaisiinireseptorille? Entä tarkoittaako myöskin TRPV täsmälleen samaa asiaa? Onko muiden alaryhmien vanilloidireseptoreilla oleellista merkitystä ihmisen kannalta kuin VR-1:llä? Entä mitä tarkoitetaan VR-1 kloonaamisella ja mitä käytännön merkitystä sillä on? Erityisesti mua kiinnostaisi vanilloidireseptorien rooli astman patogeneesissä...

Ja entistä parempaa uutta vuotta kaikille

Kommentit (8)

Volitans
Seuraa 
Viestejä10670
Liittynyt16.3.2005

Kapsaisiinireseptoreille? Kapsaisiini vaikuttaa suoraan hermosoluihin, joten mitään erityistä kapsaisiinireseptoria ei tarvita. Kapsaisiini tehoaa siksi niin limakalvoilla kuin ihollakin.

Vierailija

Aika useissakin mun lähteissä puhutaan kapsaisiinireseptoreista, ja nyt kun tajusin vielä googlettaa termillä capsaicin receptor, löytyi materiaalia rutkasti lisää. Käsittääkseni kapsaisiinireseptori olisi vanhentunut termi vanilloidireseptorille? Esim. wikin mukaan kapsaisiini kiinnittyy vanilloidireseptori-1:een ja näin ollen väittäisin, että se ei vaikuta suoraan hermosoluun, vaan vaikuttaa reseptorin kautta. Voin tosin olla väärässäkin, olen vasta selvittämässä näitä asioita itselleni, joten siksi täältä kysyinkin neuvoja.

Vierailija

Etsi tietoa myös hakusanalla vanillin receptor.

CAPSAICIN

Category: Neurochemistry
Term Paper Code: 297

MCB 165
Molecular Neurobiology and Neurochemistry
May 6, 1999
Key words: chili peppers, pain, heat, analgesic

Abstract:

Chili peppers are the fruits of the Capsicum plant, and the active compound in chili peppers is a compound called capsaicin. Capsaicin is what produces the "burning" sensation felt when a chili pepper is eaten.

The receptor for capsaicin has only fairly recently been discovered to a vanillin receptor named vanillin receptor subtype 1.

This receptor is a heat-activated ion channel in the pain pathway. Since the discovery of the receptor as a part of the pain pathway, there has been further studies as to possible capsaicin analgesic properties. Capsaicin and capsaicinoids are believed to have other physiological properties beyond the scope of the pain pathway.

These properties are both positive and negative, and so are the analgesic properties of capsaicin, depending on the mechanism. Research in these other areas are limited and most of the current research has been on the analgesic properties and the pain inducing properties of capsaicin.

http://sulcus.berkeley.edu/mcb/165_001/ ... /_297.html

Vierailija
MD
Etsi tietoa myös hakusanalla vanillin receptor.

CAPSAICIN

Category: Neurochemistry
Term Paper Code: 297

MCB 165
Molecular Neurobiology and Neurochemistry
May 6, 1999
Key words: chili peppers, pain, heat, analgesic

Abstract:

Chili peppers are the fruits of the Capsicum plant, and the active compound in chili peppers is a compound called capsaicin. Capsaicin is what produces the "burning" sensation felt when a chili pepper is eaten.

The receptor for capsaicin has only fairly recently been discovered to a vanillin receptor named vanillin receptor subtype 1.

This receptor is a heat-activated ion channel in the pain pathway. Since the discovery of the receptor as a part of the pain pathway, there has been further studies as to possible capsaicin analgesic properties. Capsaicin and capsaicinoids are believed to have other physiological properties beyond the scope of the pain pathway.

These properties are both positive and negative, and so are the analgesic properties of capsaicin, depending on the mechanism. Research in these other areas are limited and most of the current research has been on the analgesic properties and the pain inducing properties of capsaicin.

http://sulcus.berkeley.edu/mcb/165_001/ ... /_297.html

Eli samalle asialle on vielä neljäskin termi, vanilliinireseptori? Olen saanut vaikutelman, että vanilloidireseptori on kuitenkin eniten käytössä. Tottakai olen etsinyt tietoa mm. internetistä ennen tänne kirjoittamistani, ongelma vaan on siinä, että eri lähteissä samasta asiasta puhutaan eri nimillä, ja tämän vuoksi halusin varmennuksen, olenko ymmärtänyt nämä perusasiat oikein.

Vanilloidireseptorilla on vähintään 4 eri alaryhmää, joista siis VR-1 on käsittääkseni oleellisin. Muiden merkityksistä en juurikaan tiedä.
Vanilloidireseptorien rooli kivun mekanismeissa on jo tiedepiireissä tuttu asia, mutta uutena on sen vaikutus astmaan, ja juuri se minua kiinnostaa.

Vierailija

En minä tiedä, enkä ole muistanut spesialisteilta edes kysyä.

Itse syön pillereitä, jotka salpaavat lipoksygenaasia sekä leukotrieenejä.

En tarvinnut viime keväänä mitään allergialääkkeitä, vaikka allergikoille olikin vaikea kevät. Aloitin, kun minulla oli sitkeää hengenahdistusta ja hengityksen vinkunaa, eikä oikein astmasumutteet auttaneet.
PEF (peak expiratory flow) laski 500 l/min -> 350 l/min.

Parin viikon syönnin jälkeen mitään muita pillereitä enkä sumutteita ole tarvinnut. En mainitse tässä nimeä, koska ei sitä edes kaikissa apteekeissa tunneta eikä kuulu viralliseen lääketieteeseen. Yliopiston apteekista olen hankkinut.

Leukotrieenisalpaajat ovat olleet jo käypä hoito astmassa vuosia ja hiljattain myös allerginen nuha tuli viralliseksi indikaatioksi.

Nehän ovat saman taudin eri variaatioita. Nykyisin allergista nuhaa kutsutaankin myös nenäastmaksi.

*************
Thorax 2004;59:257
© by BMJ Publishing Group Ltd & British Thoracic Society

REVIEW SERIES
Cough · 5: The type 1 vanilloid receptor: a sensory receptor for cough

ENDOGENOUS LIGANDS OF VR1

The lipoxygenase enzymes catalyse the conjugation of a hydroperoxide moiety with arachidonic acid to produce one of a family of hydroperoxyeicosatetraenoic acids (HPETE). In asthma, 5-lipoxygenase produces 5-HPETE which is the precursor of the leukotrienes. However, there are a number of other lipoxygenase products named after the position of conjugation with arachidonic acid. In animal species from molluscs to mammals, HPETEs have been shown to regulate neurotransmission by increasing the opening probability of ion channels such as K+ channels. Patch clamping studies have shown that 12-HPETE is endowed with many of the characteristics that would be predicted for an endogenous capsaicin-like ligand. 12-HPETE strongly activates single channel currents with an identical current voltage relationship to capsaicin. As with capsaicin, Na+ and K+ ions are conducted and capsazepine blocks the opening of the channel. These studies were performed in primary culture of dorsal root ganglia of the rat and, while 12-HPETE was the most potent putative ligand, other lipoxygenase products including LTB4 were also active. More recently we have shown that another lipid derivative, N-arachidonoyl-dopamine (NADA), activates VR1 in different animal models and also at the recombinant human VR1 more potently than anandamide and lipoxygenase derived molecules. However, it is not known whether NADA is the most potent endogenous ligand of human VR1.

Inflammatory stimuli—including prostaglandins, bradykinin, nerve growth factor, and others—have been shown to upregulate the expression and function of VR1 via the activation of p38MAPK, PLC-{gamma}, PKC-{epsilon}, and PKA dependent pathways. Chronic airway inflammation such as that present in asthma, COPD, and other lung diseases may therefore exaggerate the sensitivity of VR1 to its agonists which, in these conditions, may reach a concentration sufficient to trigger the VR1 dependent cough reflex.

CONCLUSIONS

There is a convincing case for the promotion of VR1 as the lead candidate to be the first cloned and characterised cough receptor. The final proof must await the development of a potent and specific antagonist for use in man. It is unlikely that VR1 activation is the only stimulus for cough since some tussogenic agents such as distilled water are not inhibited by VR1 antagonism. That VR1 is a member of a growing family of structurally similar ion channels suggests a heterogeneous system which will require further dissection if we are to understand the biochemical basis of cough in health and disease.

Figure 1 The putative type 1 vanilloid cough receptor (VR1) illustrating possible regulation by inflammatory mediators capsaicin and protons. AA = arachidonic acid; HPETE = hydroperoxyeicosatetraenoic acid; PLA2 = phospholipase A2.

http://thorax.bmj.com/cgi/content/full/59/3/257/F1

Vierailija

Nyt alkaa dilemmat pikku hiljaa selkiytyä, mutta edelleen mietityttää tuo reseptorin kloonaaminen, mitä se on, ja miksi se on niin tärkeää?

Vierailija

cloning = make a copy

Kloonatessa saadaan suuri määrä reseptoreita, joita sitten voidaan tutkia perusteellisemmin, alatyyppeja etc. ja kehitellä lääkettä, joka salpaisi sen.

Kloonaus metodeista esim. PCR = Polymerase Chain Reaction

PCR-metodi suomeksi selitettynä
http://users.ugent.be/~avierstr/principles/pcr.html
http://en.wikipedia.org/wiki/Polymerase_chain_reaction

Receptor cloning and heterologous expression--towards a new tool for drug discovery.

* Luyten WH,
* Leysen JE.

Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.

The explosion in the number of cloned receptors presents the pharmaceutical industry with challenges to discover new drugs targeting those receptors; to find more-selective drugs for all novel receptor subtypes; and to learn more about the function of the receptors in order to discern the conditions where such drugs may be applied usefully as therapeutics. At the same time, receptor cloning affords an unprecedented opportunity to address these challenges: heterologously expressed recombinant human receptors can be used for drug screening and - through an improved understanding of structure-function relationship - possibly for drug design, while the receptor clones permit mobilization of the full power of molecular biology to elucidate the function of the receptors in health and disease.

PMID: [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

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