Caffeine Pharmacology

Caffeine is a naturally ocurring substance in many plants like guarana, cacao beans, cola nut but can be artificially manufactured. To understand how this substance reacts its, important to note the chemical aspects of the compound; chemically, it is a methylzantine which means that it's structure is derived from guanine, hypoxanthine and xanthosine by different methods. These analogs derived from these compounds are commonly used as psycho-stimulants because of their diferent effects on the body, and as it could be noted these could be used to oppose the actions of adenosine (what makes you sleepy) by increasing alertness in the central nervous system. Those groups that are methylated (like caffeine, for instance) stimulate the heart rate and force of contraction. Now for a little science on how they do it, these cause the release of cathecolamines stimulating adenosine receptors (A1 and A2a) and block inhibitory neurotransmitter adenosine (an inhibitor) by inhibiting phosphodiesterase resulting in increased intracelular cyclic adenosine monophosphate (cAMP). (Pohler, 2010) The following image shows the pathway:

Image extracted from http://www.sivabio.50webs.com/amp.htm; this shows adenosine interaction whith a receptor protein, blocking the production of cAMP.

A1 and A2a receptors are G coupled proteins. Their properties are rather dissimliar, A1 receptors once active lead to the inhibition of adenylyl cyclase and some types of Ca2+ sensitive channels which cause the inactivation of celular activity (or depolarization of action potentials). A2a receptors once active production of adenylyl cyclase. The distribution are diverse; since A1 are found in crainial areas that are in the hippocampus, cerebral cortex, and certain thalamic nuclei and A2a receptors are found in some glial cells, nucleus accumbens and globulus pallidus. A1 are co localized with D1 (dopamine) receptors, A2a receptors are localized with D2 (dopamine) receptors that interact with the release of GABA (an inhibitory neurotransmitter) that blocks the release of GABA in the globus pallidus. (Pohler, 2010)

Figure 2: Structural resemblance between adenosine and caffeine. It can be observed that because their similarities they would compete for the same receptor.

Caffeine contains the properties to become 100% bioavaiable by oral administration. It's later metabolized by the liver. cAMP is known as a messenger that is associated to several biochemical processes. This secondary messenger is know for it's regulation of glycogen, sugar and lipids. It activates protein kinase A (PKA) which in turn phophorylates substrate proteins. These phosphorylations are like a switch which turn "on" other functions like enzymes that convert glycogen into glucose, enzymes that increase smooth muscle contraction (like your heart) and transcription factors that regulate gene expressions.(Al-Saleh, 2010)

 To sumarize what you just read, caffeine acts as a non-selective "brake" for adenosine. This means that there will be more cAMP available to "activate" or "switch on" your body.

Now, how does this compound affect other functions? Let's evaluate it's effects on a hormonal level; in other words, the pituitary gland. The pituitary gland is a small gland found at the base of the skull made of endocrine tissue. The pituitary is known to regulate several physiological processes like stress, reproduction and even growth. Since your brain on caffeine is activated similar to the way than you would if you were scared, the anterior pituitary springs to action, releasing the adrenocorticotropic hormone (ACTH). ACTH acts on various portions of the pituitary which produces and secretes the hormone epinephrine (also called adrenaline). Adrenaline acts on the body in different manners, if you think about it, once you consume too much caffeine, or had that 3rd cup you don't usually have, you begin to feel jittery, restles and anxious.An other effect that this has on the pituitary would be the release of dopamine certain portions of the brain (to be specific, the nucleus accumbens). (Costenla, 2010)