I think the rationale is historical, and I sometimes explain it to
students this way. In the 1950's, hormones were thought of as THE
chemical messengers in the body, and then Sutherland & Rall's experiment
showed that some other "second messenger" takes over inside of the cell.
http://www.beyonddiscovery.org/content/view.page.asp?I=363
http://nobelprize.org/medicine/laureates/1971/press.html
The term "second messenger" was eventually used for two things: the
messenger molecule itself, cAMP, as well as the general concept, the
second messenger system. So when additional pathways were discovered,
they were also considered examples of "the second messenger system", even
when 3 or 4 molecules were involved in the pathway, and the term "second
messenger" was sometimes used to mean "intracellular messenger", without
regard to what number it was in the pathway. I think it's in this sense
that some textbooks refer to IP3, DAG, and Ca++ as all being "second
messengers". Adding to the confusion, "second messenger" is usually used
to indicate a diffusible molecule, so DAG doesn't fit the bill, even
though it resembles IP3 in its placement in the IP3/DAG pathway. And Ca++
may act as second messenger in one pathway and as third messenger in another.
I find Boron and Boulpaep's Medical Physiology to be the best in resolving
these questions of a molecular nature. Does anyone have a copy of that?
What I tell students is that the terminology is in flux, as it always is
at a time when new discoveries are being made. (We had a similar
discussion a while back... I think it was around the question of how many
organ systems or how many tissue types there are.) I tell students to
understand the general concept and the particular pathways, but not worry
about whether to call a particular molecule a second or third messenger.
Judy Gibber
On Wed, 8 Feb 2006, Ford, Dayton wrote:
Okay. Would someone please explain to me the rationale behind referring to
calcium as the second messenger in the IP3/DAG second messenger system,
rather than IP3 and DAG. In the cAMP system, cAMP is the molecule made that
then activates a cascade of events and is thus termed the second messenger.
In almost all of the texts that I have seen (including Guyton's 11th ed.)
the second messenger is said to be "Calcium". The only text that seems to
get it right is Berne, Levy, Koeppen, and Stanton's 5th ed. Wherin it is
stated that there are THREE systems. The cAMP system (with cAMP as the
second messenger), the Calcium-Calmodulin system (with Calcium as the second
messenger), and the Membrane Phospolipid system in which IP3 and DAG are the
second messengers. Other second messengers are listed (e.g. cGMP, NO, etc.),
but in an Intro to Physiology course we tend to focus only on the two main
pathways (cAMP, IP3/DAG). I have always argued that the second messengers in
the IP3/DAG system are IP3 and DAG. These are the molecules synthesized by
the enzyme activated by the G-protein. I thus tell my students to ignore
what the text says (Fox in my case) and refer to IP3 and DAG as the second
messengers. It becomes very confusing to my students when they see the cAMP
path in their textbook as:
Receptor --> G-Protein --> Enzyme --> Second Messenger --> Cellular Cascade
While the IP3/DAG system is thus:
Receptor --> G-Protein --> Enzyme --> Intermediate Molecule?? --> Cellular
Effect --> Second Messenger --> Cellular Cascade.
Seems to me that the only textbook that has attempted to clear up this
confusion is the Berne book. Anyone want to explain the rationale behind
this confusing bit of nomenclature??
Dayton J. Ford, Ph.D.
Associate Professor of Biological Sciences
St. Louis College of Pharmacy
4588 Parkview Place
St. Louis, MO 63110
dford@xxxxxxxxxx
314-446-8463 voice
314-446-8460 FAX
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