5-HT7 receptors (5-hydroxytryptamine (serotonin) receptor 7)
Serotonin, also known as 5-hydroxytryptamine (5-HT), is a chemical in the human body that is responsible for carrying signals along and between nerves. It is mainly found in the intestines, the brain and the blood. Since its discovery in the 1940s, serotonin has been shown to be involved in almost every cognitive and behavioural human function including sleep, appetite, mood, aggression, pain, perception, and sexual behaviour [R].
The function of serotonin is regulated by several different proteins, one of them being the 5-hydroxytryptamine receptor 7 (5-HT7 receptor). The 5-HT7 receptor has only recently been discovered and is the least studied serotonin-related protein [R].
The 5-HT7 receptors have been detected in the central nervous system (CNS) areas of the human brain, and more specifically in the regions known as thalamus, hypothalamus, amygdala and hippocampus [R]. According to a series of studies that have been carried out using animal models, the presence of the 5-HT7 receptors within those brain regions demonstrate their implication in higher brain functions such as cognition, learning capability, memory and perception. The receptors also play an important role in the circadian rhythm, our internal 24-hour clock that controls the sleep/ wake cycle, but also in mood regulation, pain transmission and control of body temperature [R,R1,R2]. Interestingly, 5-HT7 receptors are also involved in the relaxation of smooth muscle cells of the circulatory system, the intestines and the reproductive system [R].
Taking into account the involvement of the 5-HT7 receptors in so many physiological processes it is not hard for one to see that the malfunction of those receptors could result in a series of health problems. The diseases that have been linked to 5-HT7 receptors are briefly presented below.
Mood disorders – Anxiety and Depression –
A series of studies that have been conducted using animal models demonstrated a strong link between the 5-HT7 receptors and the development of mood disorders such as anxiety and depression. It has been shown that administration of drugs that block the function of 5-HT7 receptors can reduce the levels of anxiety and depression. Additionally, administration of those drugs in combination with other antidepressants increases their effect on treating depression [R, R1, R2].
Autism spectrum disorders (ASD)
A large number of studies have established that autism spectrum disorders (ASD) are caused by a deficiency in the brain serotonin system [R]. The link between the 5-HT7 receptors and ASD is not very clear. However, their association to behavioural flexibility, repetitive and stereotypic behaviours, sleep and mood disorders, and epilepsy, which are all symptoms of ASD, implicates their possible involvement in the development of ASD [R].
Recent studies have shown that the levels of 5-HT7 receptors are lower in schizophrenic patients depicting a potential link between the function of 5-HT7 receptors and the development of schizophrenia [R].
The 5-HT7 receptors have also been linked to seizure activity. Studies using mouse models demonstrated that it is possible to reduce the number of seizures by using drugs that inactivate the 5-HT7 receptors [R, R1, R2].
Obsessive-compulsive disorder (OCD)
OCD is a condition characterised by intrusive thoughts that induce anxiety and repetitive behaviours. A series of studies have demonstrated that blockade or inactivation of the 5-HT7 receptors may reduce repetitive and perseverative behaviours in mouse models [R].
Drug and alcohol addiction
Recent studies have demonstrated that genetic variations of the HTR7 gene, the gene that codes for the production of the 5-HT7 receptors, are linked to alcohol and drug abuse [R]. Interestingly, behavioural testing in mice and alcohol-preferring rats suggested that administration of drugs that block the function of 5-HT7 receptors could mediate alcohol consumption and/ or reinforcement and play a role in seeking/ craving behaviour [R]. Further studies are now carried out to investigate the 5-HT7 receptors as a novel target for treating addiction.
As mentioned above, 5-HT7 receptors regulate smooth muscle relaxation in the intestines. Thus, it is possible for them to be involved in the development of gut diseases such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and enteric infections [R].
In conclusion, the 5-HT7 receptors are involved in numerous physiological processes and have, evidently, been implicated in the development of a series of disorders. This opens up numerous possibilities for the development of new individual therapies targeting the 5-HT7 receptors.
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