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Re: Fellow pharm-geeks: a question about terminology cache-monkey

Posted by Larry Hoover on April 8, 2007, at 10:35:39

In reply to Fellow pharm-geeks: a question about terminology, posted by cache-monkey on April 7, 2007, at 12:40:28

> Hi all,
> I mean the term geek affectionately, of course. I have been doing some reading about various changes in the dopamine d-2 receptor, and am realizing that I'm a little weak on some terminology.
> Are the following more or less the same? If not, what are the differences?
> * Increase in the number of receptors
> * Up-regulation of receptors
> * Increased expression of receptors
> * Increased density of receptors
> * Increased availability of receptors

There are nuances within the phrasing, but unless you're analyzing a mechanism, the differences might be moot.

An increase in number of receptors would likely represent some physical counting process, which may or may not require the physical sampling of tissues.

Up-regulation of receptors was originally a functional criterion, with one or more possible mechanisms. It's often used as an umbrella term, these days.

Increased expression of receptors typically indicates some assessment of nuclear activity, via RNA concentrations, often messenger RNA (mRNA). Receptor protein concentrations might also be used, but that's a density metric.

Increased density is the same as increased number, for all intents and purposes.

Increased availability is a functional criterion, focussing on the relative concentration of inhibitors and/or receptor cofactors. I think it would be very context-driven. For example, magnesium concentration is directly proportional to GABA-A receptors lying in their receptive conformation.

> [I'd also be interested in finding out which (if any) of these is implied by "sensitization".]

Sensitization refers to changes in the charge threshold for depolarization, i.e. the amount of current available/required for a nerve cell to fire. This can be measured by patch-clamp techniques. Repetitive firing of a neuron will often result in its sensitization, one of the underpinnings of what we know as learning. Some drugs, for example, can attach to some non-binding surface of a receptor, and change its sensitivity. An increase in sensitized receptors could lead to cellular sensitizing. Or, chloride or sodium or potassium channels get messed with, affecting depolarization. It could be due to an increase in receptor density, which might influence the time required to reach depolarization, resulting in an increased rate of firing. So, once again, there's a contextual element to the meaning, but its a functional criterion.

> Your input would be greatly appreciated.
> Regards,
> cache-monkey

Well, that's my personal understanding of things.





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