This work seeks to summarize the article,” The Expanded Biology of Serotonin” authored by Berger, Gray, and Roth. According to authors, serotonin, a neurotransmitter that modulates neural activity and neuropsychological processes, is widely used in psychiatry and neurology. It is located mostly outside the central nervous system, and the 15 receptors of serotonin are found outside as well as inside the brain. It regulates a number of biological processes including, bowel motility, cardiovascular function, bladder control, and ejaculatory latency. However, they mention that serotonin regulates some other processes as well including platelet accumulation through receptor independent, but transglutaminase-dependent covalent linkage to the cellular proteins.
Serotonin and its receptors play an important role in regulating almost all brain functions. The cloning of 15 serotonin receptors during the last two decades has been significant in understanding the serotonin functions. The creation of receptor specific knockout mice and the receptor subtype selective drugs has proved a milestone in the use of serotonin. These developments have established the importance of serotonin for many human organ systems, and regulation of energy balance and intake of food. The findings are helpful in explaining the diverse side effects of serotonergic drugs, from metabolic syndrome to diabetes as well as valvular heart diseases.
Despite the fact that majority of total body serotonin is located outside of the Central Nervous System (CNS), and that less than one in million neurons of CNS produce serotonin, almost all human behavior processes are regulated by serotonin. The behavioral as well as neuropsychological processes regulated by serotonin include perception, mood, anger, aggression, reward, memory, appetite, sexuality, and attention besides others. It is multiple serotonin receptors that modulate each behavior, and likewise, each serotonin receptors influence different brain regions. For instance, anxious behavior is modulated mainly by 5-HT1A and
5-HT2C receptors. However, 5-HT2C receptors also modulate locomotion, reward processing, energy balance, and appetite besides anxiety. This contention clearly brings out why drugs targeting a particular serotonin receptor affect multiple behavioral processes.
As for serotonin’s roles in vascular biology, it controls vascular resistance, blood pressure, homeostasis, and platelet function. The effects of 5-HT1B receptors’ activation on cerebral blood vessels lead to vasodilation, and it explains, in part, the analgesic effects of the antimigraine drugs. Platelets contain much amount of vesicular serotonin, but cannot synthesize due to the lack of an enzyme, and take serotonin from plasma. It leads to the secretion of serotonin by the platelet dense granules in the process of platelet activation and results in the platelet accumulation and hemostatis. The selective serotonin reuptake inhibitors (SSRIs) may prolong bleeding time due to the inhibition of uptake and storage of platelet serotonin. Hence, caution needs to be exercised in the case of patients having a high risk of bleeding or on anticoagulants. Data gathered suggest that treatment with SSRI leads to decrease in myocardial infarction (MI) risk.
Moreover, serotonergic drugs were highly effective in inducing weight loss, but the use of these drugs containing fenfluramine caused valvular heart disease. Hence, these drugs need to be approved for agonist action before these could be used in humans. However, it has been established that serotonin modulates a number of different aspects of cardiac functions including electrical conduction, valvular closure, and post-MI remodeling. Experiments on animals suggest that 5-HT4 antagonists help improve the cardiac function and also, block pathological remodeling in the case of congestive heart failures. Serotonin helps in controlling respiratory and breathing drive due to its effects on brainstem respiratory control centers. It also has a role in the endocrine system, metabolism, and digestion. The intestinal enterochromaffin cells release into the gut almost 95% of the body serotonin. However, serotonin acts at the time the food enters the body. The taste buds on being activated release serotonin. On food entering the gastrointestinal (GI) tract, it is modulated by serotonin. Several bowel disorders such as irritable bowel syndrome (IBS) are caused due to an imbalance in serotonin secretion, and these disorders lead to mood fluctuations. Serotonin also plays an important part in anesthetic response, pain control, and spinal nociception. It affects sexuality by increasing ejaculatory latency, delaying orgasm, and modulates micturition. Besides reproductive functions, it plays a vital role in pregnancy. The use of SSRIs during pregnancy does not lead to postpartum hemorrhage but increases the potential risk of acquiring persistent pulmonary hypertension in the infant. Thus, serotonin is not just a mood modulator, but the regulator of a variety of physiologic and pathophysiologic processes in almost all human organs.
Work Cited
Berger, Miles, John A. Gray, and Bryan L. Roth. "The Expanded Biology of Serotonin" .Annual Review of Medicine 60.1 (2009): 355-366. Print.
