Physiology and pathophysiology of the 5‐HT<sub>3</sub>receptor

Färber, L; Haus, Ulrike; Späth, M.; Drechsler, S.

doi:10.1080/03009740410006943

Cited by 82 publications

(77 citation statements)

References 20 publications

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“…5-HT 3 receptors are also thought to be important targets of alcohols and to play a role in alcohol addiction (Hodge et al, 2004;Johnson, 2004;McBride et al, 2004). Additionally, 5-HT 3 receptors modulate certain behavioral functions, including cognition, anxiety, and depression, as well as the baroreflex, carotid chemoreflex, and the Bezold-Jarisch reflex (Costall and Naylor, 2004;Farber et al, 2004;Haus et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Serotonin and Dopamine on Human 5-HT_3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model

Solt

Ruesch²,

Forman³

et al. 2007

J. Neurosci.

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Serotonin type 3 (5-HT 3 ) receptors are members of the pentameric Cys-loop superfamily of receptors that modulate synaptic neurotransmission. In response to agonist binding and unbinding, members of this superfamily undergo a series of conformational transitions that define their functional properties. In this study, we report the results of electrophysiological studies using rapid solution exchange designed to characterize and compare the actions of the high-efficacy agonist serotonin and the low-efficacy agonist dopamine on human 5-HT 3A receptors expressed in human embryonic kidney HEK293 cells. In the case of serotonin, receptor activation rates varied with agonist concentration, and deactivation occurred as a single-exponential process with a rate that was similar to the maximal rate of desensitization. Receptors recovered slowly from long desensitizing pulses of serotonin with a sigmoidal time course. In the case of dopamine, receptor activation rates were independent of agonist concentration, receptor deactivation occurred as a complex process that was significantly faster than the maximal rate of desensitization, and recovery from desensitization occurred more quickly than with 5-HT and its time course was not sigmoidal. We developed an allosteric kinetic model for 5-HT 3A receptor activation, deactivation, desensitization, and resensitization. Interpretation of our results within the context of this model indicated that the distinct modulatory actions of serotonin versus dopamine are largely attributable to the vastly different rates with which these two agonists induce channel opening and dissociate from open and desensitized states.

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Section: Introductionmentioning

confidence: 99%

Differential Effects of Serotonin and Dopamine on Human 5-HT_3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model

Solt

Ruesch²,

Forman³

et al. 2007

J. Neurosci.

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“…It is well known that 5-HT plays important physiological roles in contraction / relaxation of smooth muscle, platelet aggregation, and neuronal transmission. Receptors mediating the actions of 5-HT are now classified into seven major groups, termed 5-HT 1 to 5-HT 7 , which include a total of 14 subtypes (2). Among these receptors, the 5-HT 3 receptor possesses unique characteristics.…”

Section: Introductionmentioning

confidence: 99%

“…Among these receptors, the 5-HT 3 receptor possesses unique characteristics. This receptor is a ligand-gated cation channel that belongs to the nicotine / GABA-receptor superfamily, while all other 5-HT-receptor subtypes belong to the family of G-protein-coupled receptors (2).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome

et al. 2007

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Abstract. We examined the pharmacological profile of ramosetron, a 5-HT 3 -receptor antagonist for irritable bowel syndrome with diarrhea, comparing it with those of other 5-HT 3 -receptor antagonists, alosetron and cilansetron, and the anti-diarrheal agent loperamide. Ramosetron showed high affinity for cloned human and rat 5-HT 3 receptors, with K i values of 0.091 ± 0.014 and 0.22 ± 0.051 nmol / L, respectively, while its affinities for other receptors, transporters, ion channels, and enzymes were negligible. Dissociation of ramosetron from the human 5-HT 3 receptor was extremely slow (t 1/ 2 = 560 min), while alosetron (t 1/ 2 = 180 min) and cilansetron (t 1/ 2 = 88 min) dissociated relatively rapidly. Ramosetron competitively inhibited 5-HT-induced contraction of isolated guinea-pig colon, with pA 2 values of 8.6 (8.5 -9.0). Ramosetron given orally also dose-dependently inhibited the von Bezold-Jarisch reflex in rats, with an ED 50 value of 1.2 (0.93 -1.6) µg / kg. In addition, oral ramosetron dose-dependently inhibited restraint stressinduced defecation in rats, with an ED 50 value of 0.62 (0.17 -1.2) µg/ kg. In all of these experiments, the potencies of ramosetron were greater than those of alosetron, cilansetron, or loperamide. These results indicate that ramosetron is a highly potent and selective 5-HT 3 -receptor antagonist, with beneficial effects against stress-induced abnormal defecation in rats.

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“…These findings has led investigators to develop hypotesis regarding underlying pathophysiologics mechanisms connecting these disorders. Today IBS is viewed upon a disorder of dysregulation of the so called brain-gut axis (8,10,30,32,33,38) .…”

Section: Discussionmentioning

confidence: 99%

“…Possibles common pathogenetic mechanisms of IBS and migraine consider the role of brain-gut axis, as well as neuroimmune and neuroendocrine interactions (3,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) . Serotonin as a major neurotransmitter of the gastrointestinal tract plays a relevant role in the IBS (4,10,36) . Today IBS is viewed upon a disorder of dysregulation of the so called brain-gut axis and lines of evidence also suggest that inflammation of the gastrointestinal tract may be of great importance in the majority of subgroups of IBS patients.…”

Section: Introductionmentioning

confidence: 99%

THE PREVALENCE AND CLINICAL CHARACTERISTICS OF PRIMARY HEADACHE IN IRRITABLE BOWEL SYNDROME: a subgroup of the functional somatic syndromes

Soares

Moreira-filho

Maneschy

et al. 2013

Arq. Gastroenterol.

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-Context -The irritable bowel syndrome and primary headache are two chronic diseases characterized by symptoms of recurring pain and affect approximately 10%-20% of the general population. Objectives -To study the prevalence of primary headache in volunteers with irritable bowel syndrome in a Brazilian urban community. Methods -It was evaluated the prevalence of primary headache associated with irritable bowel syndrome in adult volunteers 330 no patients.The protocol included the Rome III criteria, international classification of Headaches, later divided into four groups: I-Irritable bowel syndrome (n = 52), II-Primary headache (n = 45), III-Irritable bowel syndrome (n = 26) and headache, and IV-Controls (207). Results -We not found significant difference in the average age of the four groups and the diagnosis of irritable bowel syndrome, primary headache and their association was more frequent in females. The frequent use of analgesics was greater in groups II and III. Conclusion -Our results suggest that irritable bowel syndrome and primary headache are also common in third world countries. The frequency in use of analgesics in association between the two entities was relevant. The identification of irritable bowel syndrome patients with different clinical sub-types could improve the therapeutics options and the prevention strategies. HEADINGS -Irritable bowel syndrome. Headache. Comorbidities.

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Physiology and pathophysiology of the 5‐HT₃receptor

Cited by 82 publications

References 20 publications

Differential Effects of Serotonin and Dopamine on Human 5-HT_3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model

Differential Effects of Serotonin and Dopamine on Human 5-HT_3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model

Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome

THE PREVALENCE AND CLINICAL CHARACTERISTICS OF PRIMARY HEADACHE IN IRRITABLE BOWEL SYNDROME: a subgroup of the functional somatic syndromes

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Physiology and pathophysiology of the 5‐HT3receptor

Cited by 82 publications

References 20 publications

Differential Effects of Serotonin and Dopamine on Human 5-HT3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model

Differential Effects of Serotonin and Dopamine on Human 5-HT3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model

Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome

THE PREVALENCE AND CLINICAL CHARACTERISTICS OF PRIMARY HEADACHE IN IRRITABLE BOWEL SYNDROME: a subgroup of the functional somatic syndromes

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Physiology and pathophysiology of the 5‐HT₃receptor

Differential Effects of Serotonin and Dopamine on Human 5-HT_3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model

Differential Effects of Serotonin and Dopamine on Human 5-HT_3AReceptor Kinetics: Interpretation within an Allosteric Kinetic Model