Arachidonic acid and pruritus

[Guest guest]

Dear All;

Thought that you might be interested in this recent report (and

accompanying commentary) on a newly discovered itch mechanism

involving the conversion of arachidonic acid to thromboxane A2. I'm

not sure whether the pruritus/itch mechanism is exactly the same in

liver disease, but it seems like a promising development that may

spur new research in the area of pruritus. It is interesting that it

again involves arachidonic acid, which I've referred to in the past

as the " Darth Vader " of omega-6 fatty acids because of its

involvement in promoting inflammation.

_____________________

J Invest Dermatol. 2007 Aug;127(8):2042-7.

Thromboxane A2 induces itch-associated responses through TP receptors

in the skin in mice.

Andoh T, Nishikawa Y, Yamaguchi-Miyamoto T, Nojima H, Narumiya S,

Kuraishi Y.

Department of Applied Pharmacology, Graduate School of Medicine and

Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

Thromboxane A2 (TXA2), a metabolite of arachidonic acid produced by

cyclooxygenase and thromboxane synthase, is thought to participate in

chronic dermatitis. This study investigated the involvement of TXA2

in cutaneous itch. An intradermal injection of U-46619, a stable

analogue of TXA2, elicited scratching, an itch-associated response,

in mice. Dose-response curve was bell shaped with a maximum effect at

10 nmol per site. The action of U-46619 was inhibited by a

coinjection of the TP antagonist ONO-3708 and was abolished by TP

receptor deficiency. TP receptor was mainly expressed in nerve fiber

in the skin and keratinocytes. Thromboxane synthase was also

expressed in keratinocytes. U-46619 increased intracellular Ca2+ ion

concentration in primary cultures of dorsal root ganglion neurons and

keratinocytes. The results suggest that TXA2 synthesized by

keratinocytes acts as an itch mediator. It may elicit itch through

the activation of TP receptors on primary afferents and

keratinocytes; keratinocytes may produce itch mediators including

TXA2. Thus, thromboxane synthase inhibitor and TP receptor

antagonists will be candidates for antipruritic medicines. PMID:

17429442.

_____________________

J Invest Dermatol. 2007 Aug;127(8):1857-9.

The pruritus receptor unit: a target for novel therapies.

Yosipovitch G.

Department of Dermatology, Wake Forest University School of Medicine,

Winston-Salem, North Carolina 27157, USA. gyosipov@...

Although the role of prostanoids in itch was actively studied a

decade ago, interest in this area has waned in recent years. Andoh et

al. (2007, this issue) demonstrate that the prostanoid thromboxane A2

elicits scratching through its TP receptor. Identification of new

itch mediators and their respective receptors within the skin will

undoubtedly be the focus of future drug development for this

distressing symptom. PMID: 17632568.

_____________________

Best regards,

Dave

(father of (22); PSC 07/03; UC 08/03)

[Guest guest]

Dear ,

First, thank you for your diligent and intelligent research and

reporting to the list. You are a treasure.

I apologize for asking this because I did read about the arachidonic

acid connection to itching. However, I forget where it comes from. You

call it the Darth Vader of omega-6 -- is it always in omega-6? Is

omega-6 fatty acids something I / we should avoid?

Right now I'm taking a combo of omega-3, -6, and -9. I do plan to

switch to just omega-3 after this bottle is finished. Does flaxseed

have omega-3 or -6? Or what?

Thanks,

Dana

dx 2-1-06, age 60 female, not Scandinavian but English, French and a

bit of ish descent (both sides)

Arachidonic acid and pruritus

Posted by: " " rhodesdavid@... rhodesdavidwl

Date: Mon Aug 13, 2007 8:10 pm ((PDT))

Dear All;

Thought that you might be interested in this recent report (and

accompanying commentary) on a newly discovered itch mechanism

involving the conversion of arachidonic acid to thromboxane A2. I'm

not sure whether the pruritus/itch mechanism is exactly the same in

liver disease, but it seems like a promising development that may

spur new research in the area of pruritus. It is interesting that it

again involves arachidonic acid, which I've referred to in the past

as the " Darth Vader " of omega-6 fatty acids because of its

involvement in promoting inflammation.

[Guest guest]

Dear Dana;

Arachidonic acid is mostly found in meat products. The Western diet

is very rich in arachidonic acid (an omega-6 fatty acid) and

relatively low in the omega-3 fatty acids eicosapentaenoic acid (EPA)

and docoashxaenoic acid (DHA). It has been suggested that this high

ratio of omega-6/omega-3 fatty acids in today's diet may contribute

to a number of inflammatory diseases:

_____________

Biomed Pharmacother. 2006 Nov;60(9):502-7.

Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic

variation: nutritional implications for chronic diseases.

Simopoulos AP

The Center for Genetics, Nutrition and Health, 2001 S Street, NW,

Suite 530, 20009 Washington, DC, USA. cgnh@...

Anthropological and epidemiological studies and studies at the

molecular level indicate that human beings evolved on a diet with a

ratio of omega-6 to omega-3 essential fatty acids (EFA) of

approximately 1 whereas in Western diets the ratio is 15/1 to 16.7/1.

A high omega-6/omega-3 ratio, as is found in today's Western diets,

promotes the pathogenesis of many diseases, including cardiovascular

disease, cancer, osteoporosis, and inflammatory and autoimmune

diseases, whereas increased levels of omega-3 polyunsaturated fatty

acids (PUFA) (a lower omega-6/omega-3 ratio), exert suppressive

effects. Increased dietary intake of linoleic acid (LA) leads to

oxidation of low-density lipoprotein (LDL), platelet aggregation, and

interferes with the incorporation of EFA in cell membrane

phospholipids. Both omega-6 and omega-3 fatty acids influence gene

expression. Omega-3 fatty acids have anti-inflammatory effects,

suppress interleukin 1beta (IL-1beta), tumor necrosis factor-alpha

(TNFalpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids do

not. Because inflammation is at the base of many chronic diseases,

dietary intake of omega-3 fatty acids plays an important role in the

manifestation of disease, particularly in persons with genetic

variation, as for example in individuals with genetic variants at the

5-lipoxygenase (5-LO). Carotid intima media thickness (IMT) taken as

a marker of the atherosclerotic burden is significantly increased, by

80%, in the variant group compared to carriers with the common

allele, suggesting increased 5-LO promoter activity associated with

the (variant) allele. Dietary arachidonic acid (AA) and LA increase

the risk for cardiovascular disease in those with the variants,

whereas dietary intake of eicosapentaenoic acid (EPA) and

docosahexaenoic acid (DHA) decrease the risk. A lower ratio of omega-

6/omega-3 fatty acids is needed for the prevention and management of

chronic diseases. Because of genetic variation, the optimal omega-

6/omega-3 fatty acid ratio would vary with the disease under

consideration. PMID: 17045449.

_____________

The omega-3 fatty acids (also known as n-3 fatty acids) EPA and DHA

replace arachidonic acid in membranes and therefore act, in part, as

arachidonic acid antagonists. This may help dampen inflammation:

_____________

Eur J Clin Nutr. 2002 Aug;56 Suppl 3:S14-9.

Polyunsaturated fatty acids, inflammation and immunity.

Calder PC, Grimble RF

Institute of Human Nutrition, School of Medicine, University of

Southampton, Southampton, UK. pcc@...

Consumption of n-6 polyunsaturated fatty acids greatly exceeds that

of n-3 polyunsaturated fatty acids. The n-6 polyunsaturated fatty

acid arachidonic gives rise to the eicosanoid family of inflammatory

mediators (prostaglandins, leukotrienes and related metabolites) and

through these regulates the activities of inflammatory cells, the

production of cytokines and the various balances within the immune

system. Fish oil and oily fish are good sources of long chain n-3

polyunsaturated fatty acids. Consumption of these fatty acids

decreases the amount of arachidonic acid in cell membranes and so

available for eicosanoid production. Thus, n-3 polyunsaturated fatty

acids act as arachidonic acid antagonists. Components of both natural

and acquired immunity, including the production of key inflammatory

cytokines, can be affected by n-3 polyunsaturated fatty acids.

Although some of the effects of n-3 fatty acids may be brought about

by modulation of the amount and types of eicosanoids made, it is

possible that these fatty acids might elicit some of their effects by

eicosanoid-independent mechanisms. Such n-3 fatty acid-induced

effects may be of use as a therapy for acute and chronic

inflammation, and for disorders which involve an inappropriately

activated immune response. PMID: 12142955.

_____________

Because there is ample omega-6 (n-6) fatty acids already in the

Western diet, the simplest way to decrease the omega-6/omega-3 ratio

is to take fish oil supplements.

Flaxseed oil does contain an omega-3 fatty acid, alpha-linolenic

acid, but this is poorly converted to EPA and DHA in the human body.

Best regards,

Dave

(father of (22); PSC 07/03; UC 08/03)