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I'm wondering exactly how ligands bind to and release from receptors. Until recently I presumed ligands were attracted to receptors through electrostatic forces with no chemical interaction involved, and that catabolic enzymes (MAO, AChE) were simply present in the extracellular fluid. I hadn't given much thought as to how they disengage, but assumed ligands were brushed off by the extracellular fluid.

However, recently, I was reading about acetylcholinergic signaling and how it can be disrupted by, and I've come to realize is that everything I thought I knew about neurotransmission may be wrong. What I've read suggests this (article linked below):

  • AChE is membrane-bound

  • AChE is part of the AChR, or just happens to be is close enough proximity that the AChE can catabolize the ligand while bound to the receptor

  • The AChR attracts ACh's positively-charged amine, which brings the acetyl group within range of AChE's reactive alcohol group. This alcohol group cleaves the acetyl group from ACh

  • It is not until the acetyl group is cleaved that the ligand disengages from the receptor

My questions:

  • Is all of this correct?

  • Are the AChR and AChE distinct? If so, how can both simultaneously interact with a single molecule given their much larger size? If not, why are they ever spoken of as different?

  • Is this sort of catabolism-mediated disengagement the case with other neurotransmitters?

  • Where can I read more about this, and what is this sort of interaction called? It's been difficult finding information on this.

Here's the source I was reading on ACh transmission: http://www.umich.edu/~essen/html/web_mod/cobra/respiration_detailed.html

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Look for the Coursera course "Drugs and the Brain" and see when it's offered next. It touches on a lot of these issues and more, and I think you would find it fascinating. Meanwhile, I'll see if I can answer some of this a bit later. –  Chuck Sherrington Jul 31 at 11:01
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This is the text used in the course. It's gone up a lot in price, but it's very helpful. –  Chuck Sherrington Jul 31 at 11:03

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