Paradoxical dose-reponse curves

Matt Jones jonesmat at
Wed Sep 27 12:21:53 EST 1995

In article <drg-260995145542 at> Duke Groebe,
drg at writes:
>Do you suppose, then, that it is open-channel blocking or desensitization
>that explains "paradoxical dose-reponse curves" by peptides?

I don't know. There wasn't really enough information in the original post
to figure out which peptides, what the response was, etc... I don't know
much about peptides, but I think most of them act at G-protein coupled
receptors. These also desensitize, and I think it's possible that high
concentrations of peptides could block channels activated by the

In my experience, desesntization (someday I'll learn how to spell it)
doesn't usually give bell-shaped curves by itself, but it could if the
state diagram of the system had certain properties. Like an extra binding
site that preferentially promotes desensitization. I think that two
binding sites, with different effects upon occupancy, are probably
necessary to explain bell-shaped curves. Usually, I think desensitization
just left-shifts the equilibrium D-R curve, and depresses the apparent
max, as you pointed out.


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