a selection of unanswered questions

Ian Musgrave Ian.Musgrave at med.monash.edu.au
Mon Jun 3 19:32:29 EST 1996

G'Day All

Margaret Fowler <101722.35 at CompuServe.COM> writes:
>From: Margaret Fowler <101722.35 at CompuServe.COM>
>Subject: a selection of unanswered questions
>Date: 2 Jun 1996 23:05:01 GMT

>[NOTE: 1 June 1996: since posting last weekend, five replies were
>received, two (Ladasky of Stanford, Alex of ?Western Australia) not
>taking the questions seriously; one from Paul S Brookes of Cambridge,
>long but with elementary replies; one short reply from Van Frank of
>?MHAFC looking at a couple of questions; and a more considered reply
>from Cornelius Krasel in Wuerzburg.

You may be having trouble getting replies as most of your list of 48 questions 
are already answered in the open literature. Few poeple will spend their time 
trying to answer a grab bag of questions whose answers can be found with a 
little effort on the part of the asker.

As I said, most of these have been answered. If you have problems with the 
existing answers, you should address them. To avoid band width wastage. I will 
briefly address a very few of them as a general illustration.
[homily snipped]

>       The following questions have never been answered satisfactorily,
>several of them never at all:-
Then indicate which have been never answered and which have not been 
satisfactorily annswered. To my knowledge, most have infact been answered 
quite nicely indeed.

[large snip]

>Question 18: How can carriers assist the passage of ions, aminoacids,
>    etc. across membrane, when the combination must be bigger than the
>    substance carried?
Why on earth do you believe this to be a problem? There are several good 
reviews on structure and function of carriers (most relating to proton 
transporters). Look up a few issues of Trends in Biochemical Sciences, which 
should be easily available. If you have problems with these theories, what 
are they?

>Question 19: Why have few or no carriers been isolated?
Several proton transporters, five glucose transporters, two monoamine 
transporters (at least). These are the ones I know of, and I deliberately 
avoid the transporter literature. How many do you want?

>Question 26: Why is it assumed that the receptors for transmitters,
>    hormones, messengers, antibodies, drugs and toxins are on the
>    surface of the cell membrane?
It is not assumed, it has been experimentally demonstrated using several 
different techniques (differental centrifugation, autoradiography, antibody 
localization etc.) for some classes of receptor (heptahelicals, growth factor 
receptors etc.) and also experimentally demonstrated that others are 
intracellular (retinoid receptors, steroid receptors). Do you have specific 
reasons why these techniques, especially when used in combination, should be 
misleading us.

>Question 27:  How valid is the use of agonists, antagonists and
>    ligands to detect receptors, instead of the transmitters, hor-
>    mones, antigens, drugs and toxins themselves?
Very. There is extensive literature validating these techniques, and any 
number of basic "methods in.." books outlining the theories and results. 
Receptors are usually "detected" using a number of ligands, (these ligands 
usually include the appropriate native hormones/neurotransmitters as well), to 
be certain of their identity. Many synthetic agonists/antagonists have been 
specificallly synthesized to be specific for a particular receptor, so why do 
you see a problem using them to "detect" these receptors in new tissues,gene 
expression experiments etc.? Goodman and Gillman is a good place to start, 
followed by T. Kennakins publictions (see especially reviews of physiology and 

[rest of article snipped]
I could reply in detail to all of the above, but the information is 
already available in the open literature (and time is too short). There are 
many more examples in your list where the answers are already known, so it is 
hard to take the entire list seriously. If you have specific problems with the 
methods/techniques used to give the answers mentioned above, what are they?

Questioning our assumptions at regular intervals is healthy for science. But 
posting a huge list of "no one has answered this" questions, when they have 
indeed been answered is not going to start a useful debate.

Cheers! Ian
Ian Musgrave Ph.D, Prince Henry's Institute of Medical Research
PO Box 5152, Clayton 3168, Australia.
Phone +61 3 550 4286 FAX +61 3 550 6125
Lab: Ian.Musgrave at med.monash.edu.au <http://www.mmcc.monash.edu.au/~ian-mu/>
Private: Reynella at werple.mira.net.au <http://werple.mira.net.au/~reynella/>

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