What enables cells to respond to changes in the concentration of a signaling ligand ?

Ahmed Abdullah

"In chemical signaling, adaptation enables cells to respond to changes in the concentration of a signaling ligand (rather than to the absolute concentration of the ligand) over a very wide range of ligand concentrations. The general principle is one of a negative feedback that operates with a delay. A strong response modifies the machinery for making that response, such that the machinery resets itself to an off position. Owing to the delay, however, a sudden change in the stimulus is able to make itself felt strongly for a short period before the negative feedback has time to kick in." -Molecular cell biology ,bruce albert
I don't understand this paragraph. can anyone clarify this ( best with example , even paraphrasing it may help) .... I have also searched the net, for negative feedback that operate in delay.... got nothing helpful.
Any help will be highly appreciated.

Pythagorean

There's all kinds of negative feedback with delay in biosystems. I'm not really sure of context, but this sounds like the desensitization of a ligand-gated channel. The language is kind of arbitrary, though.

Could you provide more context? (chapter topic, perhaps, what kind of material are you looking at?)

Ahmed Abdullah

It was trying to explain how cell respond to change in ligand concentration rather than absolute concentration, in general terms. Yap it later talks about desensitization ... but I am unsure how "negative feedback with delay" works and wondering how it helps cell to respond to change in ligand concentration.

I guessed the following may be the case, but I am not sure ... Please correct me if I am wrong.

Suppose the concentration of ligand increase from C₁ to C₂ , as a consequence (after some intermediate steps) the target (protein or enzyme) increase or decrease it's activity and elicit the response. After certain delay because of negative feedback, the response come to a halt. At this point the existing level of ligand concentration is unable to elicit a response.
But when ligand concentration increases still, it push the existing static state resulted from some sort of equilibrium- toward a response... but eventually the negative feedback take over and halt the response.
I also assume the negative feedback is strongly coupled with the ligand concentration... that is when ligand concentration falls it also withdraw certain extent of negative feedback inhibition.

Pythagorean

Ok, now it sounds like you're talking about allosteric modulation, whereby the gate had a second, inhibitory binding sit for non-ligand (i.e. for allosteric modulation)

I think, if the local concentration of ligand changes, it changes the energy landscape of the protein, which changes the on-off rates of allosteric modulators.