G'Day Folks
Matt Jones <jonesmat at ohsu.edu> writes:
>From: Matt Jones <jonesmat at ohsu.edu>
>Subject: Re: Paradoxical dose-reponse curves
>Date: 27 Sep 1995 17:21:53 GMT
>In article <drg-260995145542 at ache.pharm.pitt.edu> Duke Groebe,
>drg at prophet.pharm.pitt.edu 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
>G-protein.
>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.
>Cheers,
>-Matt
There are a couple of models for bell shaped concentration response curves.
One involves agonists stimulating a second receptor, for which the agonists
have a lower affinty, which is physiologically anatgonistic to the first
receptor. See Trends in Pharmacological Sciences (1994) Vol 15 (No 6),
178-181. and Vol 15, (No 90, pg 321-322 for further discussion. (The examples
are G-protein linked peptide receptors).
Cheers!
-------------------------------------------------------------
Ian Musgrave PhD. Prince Henry's Institute of Medical Research
Mail: PO Box 5152 Clayton, Vic 3168, Australia. FAX: +61 3 550 6125
E-mail: Ian.Musgrave at med.monash.edu.au Phone: +61 3 550 4286
