Arachidonic Acid Metabolites, Other Inflammatory Mediators and Intestinal Ion Transport

Re: Comment on paper by Dr. MacNaughton

On Mon Dec 14, Unmack wrote
Dr. MacNaughton's responses are in italics
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>Dr. MacNaughton: The COX results are interesting. Have you measured similar activities in the jejunum or ileum<

No, we have only looked at mouse colon so far. Given the "regional" differences that we have seen with the constitutive expression of other inducible enzymes, specifically iNOS, this would be very interesting to look at.

How selective are the inhibitors, SC58125 and NS-398, do you have a K_i for COX-1 and COX-2?

We have relied on papers from the respective drug companies for doses, admittedly a dangerous thing to do, since we are working in a different species from most of these previous studies. You make an excellent point, and we will have to work out the pharmacology in our own system before making concrete claims about selectivity.

What is the conductance or change in conductance during the peak response when you add bradykinin, and arachidonic acid?

In mouse colon we do not see any appreciable change in conductance with either bradykinin or arachidonic acid.

Do you have a suggestion where the cell(s) that could constitutively synthesize COX-2 are located?

Yes, we have recent immunohistochemical evidence to suggest that the "constitutive" COX-2 is expressed in subepithelial myofibroblasts.

Mon Dec 14