B R A I N S T O R M S Clinical Neuroscience Update

Molecular Neurobiology for Practicing Psychiatrists, Part 2: How Activate Second Messenger Systems

Stephen M. Stahl, M.D., Ph.D.

Issue: Chemical begins when occupancy by a is converted into an intracellular second messenger that carries the information from the neurotransmitter deep into the target neuron. For clinicians, it is this transfer of neurotransmitter information all the way to the genome that hypothetically explains the therapeutic actions of many psychotropic drugs. This also accounts for why drugs that modify neurotransmission may take time to fully develop their clinical actions.

his feature is the second neurotransmitter.2 Next month, we . The 2 best known examples in a series on molecular will show how this second messen- of second messengers are cyclic neurobiology for the prac- ger activates intracellular AMP and phosphatidyl (PI). T ticing psychiatrist. Last and transcription factors. The systems that produce these sec- 1 month’s BRAINSTORMS provided a A second messenger system in- ond messengers are also sometimes visual vocabulary of the elements in- cludes several elements: (1) the first known as the cyclic AMP second volved in translating neurotrans- messenger (neurotransmitter), (2) messenger system, and the PI second mitter-occupied receptors into genes the neurotransmitter’s receptor, (3) a messenger system, respectively. Al- expressed in the target neuron. Here second receptor called a G though the actions of a stimulatory we begin with the first step in this that interacts with the neurotransmit- are shown here, other process, namely, formation of an ter receptor, (4) an enzyme triggered types of G are inhibitory intracellular second messenger trig- into action by the interacting pair of and slow down or prevent coupling gered by occupancy of a neuronal receptors, and (5) a second messen- of the receptor with the enzyme that membraneÐbound receptor by its ger molecule manufactured by this makes the second messenger.

Overview First Messenger (Neurotransmitter)

7 7 7 7 E

Receptor E Second Messenger

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Thus, the handoff of first mes- senger to second messenger is REFERENCES BRAINSTORMS is a monthly section of The Journal of Clinical Psychiatry aimed at providing accomplished by means of a mo- 1. Stahl SM. Molecular neurobiology for updates of novel concepts emerging from the neurosciences that have relevance to the lecular cascade: neurotransmitter to practicing psychiatrists, part 1: overview neurotransmitter receptor (Figure practicing psychiatrist. of gene activation by neurotransmitters From the Clinical Neuroscience Research 1); neurotransmitter receptor to G [BRAINSTORMS]. J Clin Psychiatry Center in San Diego and the Department of protein (Figure 2); binary complex 1999;60:572Ð573 Psychiatry at the University of California San Diego. of 2 receptors to enzyme (Figure 3); 2. Stahl SM. Essential Psychopharmacol- Reprint requests to: Stephen M. Stahl, M.D., and enzyme to second messenger ogy. 2nd ed. New York, NY: Cambridge Ph.D., Editor, BRAINSTORMS, 8899 University molecule (Figure 4). ◆ University Press; In press Center Lane, Suite 130, San Diego, CA 92122.

Figure 1. Figure 2. First Messenger (Neurotransmitter)

7

7 Receptor The first messenger causes the receptor E E to change.

G Protein G G

G protein can now bind to the receptor.

Figure 3. Figure 4.

Once bound to the 7 receptor, the G 7 protein changes shape so it can bind to an enzyme capable G E of synthesizing a second messenger. G E

Once this binding takes place, the second message will be released.

Coming Next Issue PART 3: HOW SECOND MESSENGERS “TURN ON” GENES BY ACTIVATING PROTEIN KINASES AND TRANSCRIPTION FACTORS

J Clin Psychiatry 60:10, October 1999 649648