Molecular biology of serotonin (5‐HT) receptors

Peroutka, Stephen J.

doi:10.1002/syn.890180310

Cited by 89 publications

(45 citation statements)

References 105 publications

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“…It was not surprising that WT, Ser22, and Val28 5-HT 1A receptors displayed similar ligand-binding characteristics and showed no difference in coupling to the inhibition of adenylate cyclase activity. Indeed, the regions of the 5-HT 1A receptor protein which are thought to be most important for these functions are the transmembrane hydrophobic domains and their connecting loops, rather than the putative amino-terminal extracellular domain where the Ser22 and Val28 amino acid substitutions are located (Dohlman et al 1991;Peroutka 1994). Although the pharmacological and functional profiles of WT, Ser22, and Val28 receptors were similar, the long-term agonist-promoted down-regulation properties were remarkably different.…”

Section: Discussionmentioning

confidence: 99%

Agonist-Promoted Down-Regulation and Functional Desensitization in Two Naturally Occurring Variants of the Human Serotonin1A Receptor

Rotondo

Nielsen

Nakhai

et al. 1997

Neuropsychopharmacology

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We recently reported two naturally occurring polymorphisms of the human serotonin 1A receptor: glycine22 → serine (Ser22) and isoleucine28 → valine (Val28) (Kobilka et al. 1987;Chanda et al. 1993) coded by an intronless gene located on chromosome 5 at 5q11.2-q13 (Kobilka et al. 1987). Like other members of the G-protein-coupled receptor family (Dohlman et al. 1991), the 5-HT 1A receptor consists of seven transmembrane hydrophobic domains, with an extracellular aminoterminal domain and a cytoplasmic carboxyl-terminus. By coupling with the G i/o family of heterotrimeric G proteins, the 5-HT 1A receptor has been shown to either inhibit or activate adenylate cyclase activity, open potassium channels, close calcium channels, and inhibit phosphatidylinositol turnover (reviewed in Boess and Martin 1994). The 5-HT 1A receptor is expressed both presynaptically on the cell bodies and the dendrites of serotonergic neurons located in the raphe nuclei and postsynaptically with the highest density in the limbic system (Zifa and Fillon 1992;Burnet et al. 1995).The 5-HT 1A receptor is believed to play a role in a variety of behaviors, such as aggression, sexual behavior, and appetite control, and in several psychiatric disorders, such as mood disorders, anxiety disorders, anorexia ner-

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Section: Discussionmentioning

confidence: 99%

Agonist-Promoted Down-Regulation and Functional Desensitization in Two Naturally Occurring Variants of the Human Serotonin1A Receptor

Rotondo

Nielsen

Nakhai

et al. 1997

Neuropsychopharmacology

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“…This system appears primarily to be involved in modulation of sensory input and motor control. Serotonin receptors have been classified into families designated 5-HT 1-7 on the basis of their molecular biological characteristics (Hoyer and Martin 1997;Peroutka 1994;Saudou and Hen 1994). At present these have been subdivided into approximately 14 subtypes, and their number grows each year.…”

Section: Anatomy Of the Serotonin Systemmentioning

confidence: 99%

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

Meltzer

Smith

DeKosky

et al. 1998

Neuropsychopharmacology

451

237

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(5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life may contribute to behavioral changes commonly observed in the elderly population. Extensive evidence implicates a deficit in serotonergic neurotransmission in the development of major depression. It has been further suggested that the agerelated changes in 5-HT neurons may predispose the elderly to develop depression. There is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer's disease (AD), with serotonergic dysfunction potentially responsible for a significant portion of the behavioral aspects of the disease. This implication of the 5-HT system in aging and age-related cognitive and mood disorders rests in large part on post mortem studies and animal models, which are limited in their capacity to predict dynamic human biochemical-behavior relationships or to accurately model the living human brain. Initial applications of functional brian imaging with positron emission tomography (PET) in the in vivo study of the brain in aging, depression, and dementia focused on characterizing alterations in physiological measurements of cerebral metabolism and perfusion. However, recent advances in PET radiochemistry, instrumentation, and image processing have paved the way for noninvasive means to test specific hypotheses regarding the direct involvement of 5-HT neurons in the behavioralMajor depression in late life and Alzheimer's disease (AD) are disorders of enormous and increasing public health significance. The prevalence of major depression is estimated at 1% to 10% of persons 60 years of age or older, whereas depressive symptoms may occur in up to 20% (Blazer et al. 1987; Borson et al. 1986; Casey 1994). Substantially higher rates of both major and minor depressions occur among institutionalized aged persons (Parmelee et al. 1989). Furthermore, the rate of suicide in this age group is higher than at any other Address correspondence to: Carolyn Cidis Meltzer, M.D., University of Pittsburgh Medical Center, PET Facility, B-938, 200 Lothrop Street, Pittsburgh, PA 15213-2582. Received March 6, 1997 accepted October 3, 1997. 408 C.C. Meltzer et al.N EUROPSYCHOPHARMACOLOGY 1998 -VOL . 18 , NO . 6 stage of life (Casey 1994). Psychosocial issues such as bereavement, disability, and declining health may serve as contributing factors in the development of geriatric depression (Casey 1994;Gilewski et al. 1991;Kennedy et al. 1991). Ad is truly a disorder of aging, with an incidence of 5% in persons older than 65 years and doubling of disease prevalence every 5 years after age 65; affected individuals represent 20% to 50% of the population after age 80 (Cross and Gurland 1986) (Evans et al. 1989). Costs associated with dementia burden exceed $90 billion annually in the United States (Ernst and Hay 1994). Depression is commonly seen in AD patients and may further interfere with cognitive function, as well as substantially...

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“…HT2A subtype due to the attenuating action of spiperone, nall reduction on which is 1000 times more selective for 5-HT,A than 5-HT2c icor inhibition on receptors (Peroutka, 1994). This corresponds to recent evi-(c) At a higher dence suggesting a high level of 5-HT,A receptor mRNA prese to 5-HT was sent in the dorsal motor nucleus of the vagus of the rat % reduction was (Pompeiano et al, 1994;Wright et al, 1995) and also, to in vivo work where 5-HT increases spontaneous activity of antidromically identified DVMs via a 5-HT2A 2C receptor (Wang et al, 1995a Wang et al, 1995b).…”

Section: -Ht 20 Tmmentioning

confidence: 99%

The effect of 5‐HT and selective 5‐HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro

Albert

Spyer

Brooks

1996

British J Pharmacology

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1 Whole-cell patch-clamp recordings were made from 142 visually identified rat dorsal vagal preganglionic neurones (DVMs). Applications of 5-hydroxytryptamine (5-HT, 20 guM, 2 min) elicited a slow depolarization (8.2 + 0.5 mV, n = 59) in 95% of the cells tested, accompanied by an increase in excitability. In (68%) of DVMs the depolarization was associated with an increase in apparent membrane resistance (Rm, 22.7+2.2%). These depolarizations and increases in Rm (14.3+2.6%, n=8) were maintained in a medium which blocked synaptic transmission. LY 53,857 (1 gM) and the 5-HTIA/2A receptor antagonist, spiperone (1 jgM). The 5-HTIA receptor antagonist, pindobind 5-HTlA (5 gM), had no effect on the depolarizing response to 5-HT.4 The effect of 5-HT was mimicked by the 5-HT2A,2c receptor agonist, a-methyl-5-HT (50 uM), the 5-HT, receptor agonist, 5-carboxamidotryptamine (20 jIM) and the putative 5-HT4 agonist, 5-methyoxytryptamine (50 pM). The selective 5-HT4 receptor antagonist, GRI13808, had no effect on the depolarizing effect of 5-HT or 5-MEOT on DVMs.

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Molecular biology of serotonin (5‐HT) receptors

Cited by 89 publications

References 105 publications

Agonist-Promoted Down-Regulation and Functional Desensitization in Two Naturally Occurring Variants of the Human Serotonin1A Receptor

Agonist-Promoted Down-Regulation and Functional Desensitization in Two Naturally Occurring Variants of the Human Serotonin1A Receptor

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

The effect of 5‐HT and selective 5‐HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro

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