This chapter is related to the aims of Section C(iv) from the 2023 CICM Primary Syllabus, which expects the exam candidate to "explain receptor activity with regard to... second messengers and G proteins".
This has only appeared in the past papers once, but - given how few pharmacodynamics questions there are - that gives it a substantial percentage share of the total. Question 2 (p.2) from the second paper of 2007 asked the candidates to "describe the term second messenger". An accurate answer would report that "second messenger" is a compound two-word term, one of the most common technical glossary item employed to give more precision than either word alone would have, not being exact synonyms. However, judging from the college answer they expected the candidates to define the term instead. It is easy to miss these subtle differences.
For published literature on this subject, one cannot go past the (free, online) Chapter 20 from Molecular Cell Biology (Lodish, 2000). If one has institutional access or money, one may make use of Goodman and Gilman's Chapter 3 (which lists the systems but offers little in the way of definition). Once one gets to a certain point of sophistication, the definition for certain terms probably becomes assumed intuitive knowledge (eg. this article from Spindel, 2005)
The college definition from the answer to that one SAQ on this topic is somewhat lacking, insofar as it fails to define the term in a scientific-sounding way.
"... receptor binding is coupled to a subsequent series of intracellular biochemical events that precipitate the ultimate hormone/drug effect"
is what they came up with. The failure to generate a satisfactory definition is no fault of the examiners, as different definitions can be found in just about every medical dictionary. A whole selection can be reproduced for comparison:
"...an intermediary molecule that is generated as a consequence of hormone receptor interaction"
"...a chemical substance inside a cell that carries information farther along the signal pathway from the internal part of a membrane-spanning receptor embedded in the cell membrane"
"...any of various intracellular chemical substances...that transmit and amplify the messages delivered by a first messenger to specific receptors on the cell surface"
To add to the growing list of unsatisfactory definitions would be negligently wasteful of the trainee's time, and therefore well in the spirit of this website. One could, therefore, describe a second messenger as an intermediate molecule for an intracellular signal transduction cascade, which is used to transmit and amplify the signal between an extracellular stimulus and an intracellular effector. These molecules were discovered in the late 1960s by Earl W. Sutherland's group, who received a Nobel Prize in Medicine for their experiments. The term was coined around that era, to discriminate the intracellular signal transduction pathway mediators from the "first messenger" hormones such as glucagon or adrenaline.
The basic characteristics of a second messenger system can be summarised for exam purposes as follows:
It is possible to classify the second messenger systems into several broad types:
These are perhaps best dealt with in their own chapters.