Saturday, 14 December 2013

The Effects of Hormone Serotonin (2)

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter derived from tryptophan,  primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). In Gut, serotonin regulates intestinal movements, in CNS, it regulates mood, appetite, sleep, memory and learning, etc.
11. Serotonin circuits and anxiety
Fear, a reaction to a threatening situation, is a broadly adaptive feature crucial to the survival and reproductive fitness of individual organisms. By contrast, anxiety is an inappropriate behavioral response often to a perceived, not real, threat. In the study by The Salk Institute for Biological Studies functional imaging, biochemical analysis, and lesion studies with humans have identified the HPA axis and the amygdala as key neuroanatomical regions driving both fear and anxiety. Abnormalities in these biological systems lead to misregulated fear and anxiety behaviors such as panic attacks and post-traumatic stress disorders. These behaviors are often treated by increasing serotonin levels at synapses, suggesting a role for serotonin signaling in ameliorating both fear and anxiety. Interestingly, serotonin signaling is highly conserved between mammals and invertebrates(11).

12. Serotonin in Alzheimer's disease
Mounting evidence accumulated over the past few years indicates that the neurotransmitter serotonin plays a significant role in cognition. In the study by Northeast Ohio Medical University researchers indicated that as a drug target, serotonin receptors have received notable attention due in particular to the role of several serotonin-receptor subclasses in cognition and memory. The intimate anatomical and neurochemical association of the serotonergic system with brain areas that regulate memory and learning has directed current drug discovery programmes to focus on this system as a major therapeutic drug target. While many of these compounds will likely find application as adjuvant therapy in the symptomatic treatment of Alzheimer's disease, there are currently only a few drug entities with activity against serotonin receptors that may offer the potential to alter the progression of the disease(12).

13. Biosynthesis and the development of Parkinson's disease and schizophrenia

In the study of Somatic transposition in the brain influences the biosynthesis of metabolites involved in Parkinson's disease and schizophrenia, researcher shows that somatic transposition in the human brain can influence the biosynthesis of more than 250 metabolites, including dopamine, serotonin and glutamate, shows large inter-individual variability in metabolic effects, and may contribute to the development of Parkinson's disease and schizophrenia.

14. Serotonin and vasoconstrictor synergism
In the study to observe the Contractile synergism between serotonin (5-hydroxytryptamine, 5-HT) and other vasoconstrictor substances  in a number of peripheral and cerebrovascular blood vessels, found that this phenomenon may play an important role in certain pathological states such as hypertension, peripheral vascular disease, and coronary spasm. Tthe synergism between serotonin and other vasoconstrictor agents and focus on a recently described type of vasoconstrictor synergism in which precontraction with a non-5-HT receptor agonist yields an enhanced contractile response to serotonin which is mediated by previously inactive or "silent" 5-HT receptor subtypes(14).

15. Serotonin and arterial vessels
The vasodilator effects of serotonin can be caused by (a) inhibiting vascular smooth muscle directly, (b) releasing other inhibitory substances, such as vasoactive intestinal polypeptide, (c) inhibiting adrenergic neurotransmission, and (d) triggering of endothelium-dependent relaxation, according to the study by J Cardiovasc Pharmacol. 1984;6 Suppl 2:S421-8(15).

16. Serotonin and vascular reactivity
In the study of Serotonin causes of contraction of the vascular smooth muscle cells in most blood vessel, found that at low concentrations serotonin amplifies the vasoconstrictor responses to other vasoactive substances. Ultimately the effect of serotonin on vascular constriction is defined by the balance between these different actions. In the intact organism under normal conditions serotonin may play a modulatory role but exacerbation of the contractile effects because of hypersensitivity of the smooth muscle cells, local physical or humoral factors or loss of the relaxatory ability may lead to abnormal tissue responses. Thus, serotonin-induced vasoconstrictor responses may play a role in the etiology of vasospasm and peripheral vascular diseases, in particular at sites of endothelial lesions(16).

17. Serotonin and the blood vessel wall
Serotonin has complex effects on the cardiovascular system. In the intact animal it may cause increases or decreases of blood pressure and in isolated blood vessels contraction or relaxation depending on the species and vascular bed studied, the route of administration and the dosage used. According to the study by Dr. Vanhoutte PM and Dr.  Lüscher TF. serotonin may act indirectly by amplifying the response to norepinephrine and other agonists, by displacing norepinephrine from adrenergic nerve terminals or releasing constrictor substance(s) from the endothelium. Dilatation in response to serotonin is mediated by endothelial and prejunctional S1-serotonergic receptors which pharmacologically resemble 5-HT1-binding sites. In hypertension, constrictor responses to serotonin are augmented, while the vasodilator effects of the monoamine are decreased. The constrictor response to serotonin is increased more than those to other agonists, suggesting a functional rather than a structural adaptation of the hypertensive blood vessel wall. In hypertension the turnover of circulating platelets, the major source of peripheral serotonin, is accelerated and the mechanisms for the removal of the monoamine are impaired. The functional changes of the blood vessel wall and platelets could play a role in the maintenance of the increased peripheral vascular resistance in chronic hypertension, and they could be involved in the pathogenesis of complications of the hypertensive process(17).

18. Cardiovascular effects of serotonin
Serotonin causes contraction of most large arteries and veins; it also causes contraction of venules. This is due mainly to direct activation of vascular smooth muscle, although amplification of the response to other endogenous vasoconstrictors (e.g., angiotensin II and norepinephrine) as well as facilitated release of norepinephrine may contribute. In peripheral blood vessels, the receptors mediating the contractions evoked by serotonin belong mainly to the 5-HT2-serotonergic subtype; in the coronary and cerebral arteries, this need not be the case. Vasodilator responses to serotonin are seen mainly at the arteriolar level, but they can also be observed in larger blood vessels. They can be caused by the release of other endogenous vasodilators (e.g., vasoactive intestinal polypeptide), direct relaxation of vascular smooth muscle, inhibition of adrenergic neurotransmission, or production of endothelium-derived relaxing factor(s). The dilator responses to serotonin are mediated by receptors with characteristics similar to 5-HT1-serotonergic binding sites. Aggregating platelets release enough serotonin to evoke both constrictor and dilator responses. The absence of endothelium may change the primary response to aggregating platelets from relaxation to contraction. The responsiveness of the blood vessel wall to serotonin can be augmented acutely by local hypoxia or by cooling(18).

19. Correction of altered serotonin exchange in adolescents with functional disorders of digestive system
In the searching for the ways of improvement treatment of functional pathologies of the system of digestion an author is studied the concentration and the role of serotonin in 180 adolescents, showed that serotonin receptors 5HT1 agonists were used for patients with paroxysms of abdominal pain mainly at neurocirculatory disfunction and migraine(19).

20. Serotonin and Fibromyalgia and migraine
In the study  of fibromyalgia sufferers randomly administered a combination of monoamine-oxidase inhibitors (MAOIs)-A/B with 5-HTP, 5-HTP alone, MAOIs-A/B alone, or the tricyclic drug amitriptyline in order to compare the efficacy of these treatments, showed that high prevalence of migraine in the population of fibromyalgia sufferers, suggests a common ground shared by fibromyalgia and migraine. Migraine has been demonstrated to be characterized by a defect in the serotonergic and adrenergic systems. A parallel dramatic failure of serotonergic systems and a defect of adrenergic transmission have been evidenced to affect fibromyalgia sufferers too. Enhancing serotonergic analgesia while increasing adrenergically mediated analgesia seems to be an important tool in fibromyalgia(20). 

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