MadSci Network: Biochemistry

Re: possible way to stop capsaicin bonding with VR1

Date: Thu Sep 25 11:10:13 2003
Posted By: Steve Mack, Post-doc/Fellow, Molecular and Cell Biology
Area of science: Biochemistry
ID: 1062881050.Bc

Hi Taylor,

Thanks for the great question. It sounds like you already know a fair bit about the action of capsaicum, so I won't go into to much background except to say that the vanilloid receptor-1 (VR1) moelcule normally functions to detect dangerously high temperature extemes, so when we talk about blocking the binding of VR1, we need to think about retaining the important temperature-sensitive function of this receptor.

In general, the easiest way to stop capsaicin from binding to the VR1 moelcule is to wash it away from VR1 with a non-polar solvent like milk or yogurt. As a lover of spicy Thai food, I've noticed that it helps to eat lettuce after getting a mouth-full of capsaicum, so there may be something in lettuce that blocks capsaicum or stimulates its release from VR1.

Speculation aside, there do seem to be some molecules that interact with the VR1 molecule to block the action or binding of capsaicum. Capsazepine is a competetive inhibitor of VR1, which means that it binds to the same site as capsaicum, and physically blocks capsaicum's access to the VR1 molecule. In addition, a molecule with the rather unwieldy name of N-(4- Tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine -1(2 H)-carbox-amide (known more simply as BCTC) has been shown to competitively inhibit VR1 as well. BTCT is similar in stricutre to capsazepine, but has some additional effects on VR1. For example, it inhibits the activity of VR1 in response to low pH conditions, something that capsazepine does not do.

Thapsigargin has long been known as an ATPase, and has recently been shown to bind to the VR1 receptor, blocking its action in the presence of capsaicum. It looks like thapsigarin works by directly affecting VR1 and perhaps also by blocking capsaicum's ability to bind through competitive inhibition.

These are just a few examples of molecules that can be used to regulate VR1 activity in relation to capsaicum. There are probably more, but I think you get the idea. I'm going to list some references for these molecules below. They might be too technical for you, but you seem to have a good understanding of VR1 and capsaicum, so you should take a look if you are curious. Overall, it seems unlikely that these compounds will be available for general consumption anytime soon, so the best way to stop capsaicum from binding to VR1 for the foreseeable future is to wash your spicy food down with some milk.

Toth A, Kedei N, Szabo T, Wang Y, Blumberg PM (2002) Thapsigargin binds to and inhibits the cloned vanilloid receptor-1. Biochem Biophys Res Commun. May 3;293(2):777-82.

Valenzano KJ, Grant ER, Wu G, Hachicha M, Schmid L, Tafesse L, Sun Q, Rotshteyn Y, Francis J, Limberis J, Malik S, Whittemore ER, Hodges D. (2003) N-(4-tertiarybutylphenyl)-4-(3- chloropyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: I. in vitro characterization and pharmacokinetic properties. J Pharmacol Exp Ther. Jul;306(1):377-86. Epub 2003 Apr 29.

Pomonis JD, Harrison JE, Mark L, Bristol DR, Valenzano KJ, Walker K. (2003) N-(4- Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: II. in vivo characterization in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. Jul;306(1):387-93. Epub 2003 Apr 29.

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