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Neurotransmitter questions

Joshua W. Fost jwfost at phoenix.Princeton.EDU
Tue Oct 13 15:56:48 EST 1992

In article <1aqqt4INNi4c at calvin.usc.edu> alves at calvin.usc.edu (William Alves) writes:
>First, this whole neurotransmitter business. As I see it, there are only
>two possible effects a neurotransmitter can have on a neuron - it can
>inhibit or excite the cell. Then doesn't it seem logical that there would
>be only two types of neurotransmitters, instead of the pharmacopeia that
>has been discovered? What is the difference between inhibition from one
>neurotransmitter and another?
>Second, the non-technical sources I have read have made a big deal out of
>the chemical similarities between certain hallucinogens (LSD for example)
>and certain neurotransmitters (serotonin for example). Yet is simple 
>mimickry behind all of the drug's effects? If that is so, why do different
>serotonin-like drugs have wildly different effects, and others have none
>at all?

First of all, there are *not* only two effects NTs can have on cells.
Many receptors are coupled to so-called 2nd messengers which can 
produce all kinds of funky effects. For example, GABA, perhaps the
most common inhibitory NT in the CNS, has a class of receptors which
produce only small inhibitory PSPs (post-synaptic potentials) but 
which are coupled to several other proteins which can modulate the
amount of an intracellular protein called adenylate cyclase. It turns
out that adenylate cyclase can then go on to change the amount of
transmitter that is released from that cell, and this transmitter need
NOT be GABA. 2nd messengers can also go to the nucleus of the cell
and change gene readout, which can, in principle, do absolutely
	Furthermore, all PSPs are not created equal. That is, the
time course and magnitude of a given IPSP, for example, can vary a lot,
and such variation can really affect how signals are integrated in a
given post-synaptic neuron. How do you vary the time course and
magnitude of a PSP? Well, you do it by using a different receptor.
	So, there are all kinds of weird and subtle things that come out
of the interaction between NT and receptor. Who knows WHY the brain
needs all these mechanisms. (Well, one could speculate.) The fact is,
if you can think of ten ways in which the brain might be doing
something, it is doing it in all ten, plus ten that you haven't thought
of yet.

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