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From:
Christina Wahl <[log in to unmask]>
Reply To:
Informed Discussion of Beekeeping Issues and Bee Biology <[log in to unmask]>
Date:
Tue, 26 Mar 2013 21:38:24 -0400
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Dear Pete,

Please consider that I would not be disputing what you say, if you were not missing something BASIC here, and that is why I suggested that you "learn receptor physiology".

Perhaps we should have an online tutorial!

Let's start!

1.  Acetylcholine receptors are nervous system receptors located between neurons, and they are also found between nerve cells and skeletal muscle (i.e., "neuromuscular synapses").
2.  Acetylcholine receptors occur in several "flavors", including "nicotinoid" receptors, named because the first ones found were observed  to bind nicotine as an agonist (an artificially introduced ligand) in addition to acetylcholine (what they naturally bind to).  The other major class of acetylcholine receptor is named for its affinity to a chemical found in mushrooms and is accordingly named "muscarinic" because those receptors have an additional affinity to muscarine as well as acetylcholine.
3.  All neuronal, and neuromuscular, receptors cause excitation or inhibition postsynaptically.  This is their FUNCTION and it is independent of their receptor binding AFFINITY.  This is an essential point!
4.   Activation of postsynaptic membranes by neurotransmitters like acetylcholine initiate either graded responses or action potentials at the postsynaptic neuron or muscle cell (the latter only contracts in response).
5.  This is true of all of them....insect and vertebrate.  AN IMPORTANT POINT!
6.  Selectivity differs, because membrane-bound receptors are NOT ENZYMES!  This is not the same as metabolism of "ethanol vs. methanol".  Life is beautiful!  Signaling is complex, and acetylcholine receptors are not as specific as many enzymes.  They can be activated by other, similar, compounds...like nicotine, or "neonics", for which they have varying AFFINITIES.
7.  Clever biochemists discovered molecules that more vigorously activate insect nicotinic ACh receptors than vertebrate nACh receptors (i.e. they have a greater affinity for insect ones, see the MSDS data to confirm that vertebrate responses are similar at high doses)...and neonic pesticides were BORN!  This is called "selective affinity".

Pete, I'd still be very happy to lend you a book on the subject.  There is a lot more to learn here.  It's why we study the subject for months and why we get course credits in college for topics like "neurophysiology".

Christina
________________________________________
From: Peter Loring Borst [[log in to unmask]]
Sent: Tuesday, March 26, 2013 8:47 PM
To: [log in to unmask]
Cc: randy oliver; Christina Wahl
Subject: the difference between nicotinoids and neonicotinoids

Christina writes:
> But please, you really don't understand receptor physiology.

Contrary to what has been stated, I understand the difference between nicotinoids and neonicotinoids, and the fact that they are specific to vertebrate and inverterbrate nAChRs respectively. I base this upon work done by researchers at UC Berkeley, by scientists whose careers depend upon understanding these distinctions. I may be wrong, but are they? How do you reconcile what you are saying with this:

Neonicotinoid insecticides display excellent selectivity profiles that are largely
attributable to specificity for insect versus mammalian nAChRs.

Neonicotinoids and nicotinoids have common structural features but
different protonation states at physiological pH. The neonicotinoids (e.g., IMI) are
not protonated and selective for the insect nAChR, whereas the nicotinoids (e.g.,
nicotine) are cationic in nature and consequently selective for the mammalian
nAChR. Therefore, neonicotinoids and their analogs are excellent probes to help
define the mechanisms of selectivity and ultimately the topological divergence
between insect and vertebrate binding sites.

NEONICOTINOID INSECTICIDE TOXICOLOGY: Mechanisms of Selective Action
Motohiro Tomizawa and John E. Casida
Environmental Chemistry and Toxicology Laboratory, Department of Environmental
Science, Policy and Management, University of California, Berkeley, California 94720-3112

Peter

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