54739-18-3CJOFXWAVKWHTFT-XSFVSMFZSA-NCJOFXWAVKWHTFT-XSFVSMFZSA-N
Fluvoxamine1-Pentanone, 5-methoxy-1-[4-(trifluoromethyl)phenyl]-, O-(2-aminoethyl)oxime, (1E)-
DTXSID2044002PR:000015189sodium-dependent serotonin transporterCL:0000300gametePCO:0000001population of organismsC82476spawningUBERON:0003978valveGO:0098810neurotransmitter reuptakeGO:0051610serotonin uptakeGO:0001820serotonin secretionGO:0048469cell maturationGO:0050881musculoskeletal movementGO:0022414reproductive process2decreased1increased6prematureFluoxetine2016-11-29T18:42:272016-11-29T18:42:27Fluvoxamine2016-11-29T18:42:272016-11-29T18:42:27WCS_396373bivalves31199Argopecten irradians6596Mercenaria mercenaria59239Arctica islandica6584Spisula solidissima47528Anodonta cygneaWCS_45954Dreissena polymorphaInhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)Molecular<p>Inhibitors of the serotonin reuptake transporter (SERT; 5-hydroxytryptamine transporter; 5-HTT) block the reuptake of the neurotransmitter serotonin, increasing its residence time in synapses.
</p><p><em>
Toxcast assays that target the serotonin transporter (5-HTT; SERT) gene SLC6A4 include:
NVS_TR_rSERT,NVS_TR_rSERT.
</em>
</p>CL:0000100motor neuron2016-11-29T18:41:252017-09-16T10:15:51Increased, serotonin (5-HT) Increased, serotonin (5-HT) Cellular<p>Increased concentration of serotonin in neuronal junctions either due to increased release of serotonin or diminished reuptake.</p>
CL:0000100motor neuron2016-11-29T18:41:252017-09-16T10:15:52Increased, oocyte maturationIncreased, oocyte maturationOrgan<p>change in oocyte electrical state, initiation of the germinal vesicle break down (GVBD), and progression from prophase to metaphase [<a href="#_ENREF_66" title="Fong, 1994 #239">66</a>, <a href="#_ENREF_69" title="Hirai, 1988 #233">69</a>, <a href="#_ENREF_76" title="Alvarado-Alvarez, 1996 #281">76</a>, <a href="#_ENREF_82" title="Osanai, 1988 #286">82</a>]. </p>
<p>bivalves</p>
<p>Fong 1994, Hirai 1988, alvarado-alvarez 1996, Osanai 1988</p>
2016-11-29T18:41:302017-01-17T00:55:31Increased, PopulationIncreased, PopulationPopulation2016-11-29T18:41:302016-12-03T16:37:53induced spawninginduced spawningIndividual2017-01-13T15:38:172017-01-13T15:38:17Increased, valve movementIncreased, valve movementTissue<p>In bivalves, the muscle involved in valve movement is the anterior byssus retractor muscle (ABRM). This muscle and other muscles can undergo a catch state of contraction, which is characterized by a very slowly decaying force in the absence of stimulation. When contraction of the ABRM (and other catch-capable muscles) is initiated by the neurotransmitter acetylcholine, it contracts actively and remains in the contracted state with minimal energetic investment (Güth et al. 1984; Butler et al. 1998) even after the acetylcholine stimulation has ceased and internal calcium stores are returned to basal levels(Ishii et al. 1989). This unique physiology allows the muscle to maintain a closed valve without depleting energy reserves. In mollusks, the catch state is terminated by serotonin.
</p>Not Specified2016-11-29T18:41:302016-12-03T16:37:53Increased, Reproductive SuccessIncreased, Reproductive SuccessIndividual2016-11-29T18:41:302016-12-03T16:37:53Increase, cilia movementIncrease, cilia movementTissue<p>Cilia in the gills and pedal of mollusks are under serotonergic control. Serotonergic neurotransmission results in increased levels of cAMP which, in turn, activate protein kinase A (PKA). PKA phosphorylates Serine and threonine residues, which directly increases or decreases the activities of numerous proteins. PKA also activates CREB which binds the cAMP response element, altering downstream gene transcription. In the bivalve Mytilus galloprovincialis, two isoforms of PKA have been identified with regulatory subunits R(myt1) and R(myt 2). The isoform with R(myt2)appears to mediate cAMP control over cilia beat frequency(Bardales et al., 2011).</p>
<p><em>Cilia beat frequency (CBF) may be measured by use of video microscopy. Schmid et al., 2006 measured CBF by infrared differential interference contrast (IR-DIC) video microscopy. </em></p>
<p>Bardales, J. R., J. L. Cascallana and A. Villamarín (2011). "Differential distribution of cAMP-dependent protein kinase isoforms in various tissues of the bivalve mollusc Mytilus galloprovincialis." Acta Histochemica 113(7): 743-748.</p>
<p>Schmid, A., G. Bai, N. Schmid, M. Zaccolo, L. E. Ostrowski, G. E. Conner, N. Fregien and M. Salathe (2006). "Real-time analysis of cAMP-mediated regulation of ciliary motility in single primary human airway epithelial cells." Journal of Cell Science 119(20): 4176-4186.</p>
2016-11-29T18:41:252017-01-13T16:27:4212fbf2ac-fbac-467e-aa9f-f8e8007e5a3ea33dd959-8edd-417a-a5eb-3b1b59f985b62016-11-29T18:41:372016-12-03T16:38:05478e7b19-524c-4c15-8dea-5fc2ce50f76d44d61ff4-a72a-4253-95ac-1617f6657c362016-11-29T18:41:372016-12-03T16:38:050ed5da14-b028-496c-8fc3-0bf81c5c1b3012fbf2ac-fbac-467e-aa9f-f8e8007e5a3e2016-11-29T18:41:342016-12-03T16:37:5812fbf2ac-fbac-467e-aa9f-f8e8007e5a3e109fd084-93d2-4cc7-b667-939bb034b9552017-01-17T01:02:162017-01-17T01:02:16a33dd959-8edd-417a-a5eb-3b1b59f985b6ce8b92dd-81b6-411a-87a8-f85a24bda3582017-01-17T01:02:382017-01-17T01:02:38109fd084-93d2-4cc7-b667-939bb034b955ce8b92dd-81b6-411a-87a8-f85a24bda3582017-01-13T15:44:432017-01-13T15:44:43ce8b92dd-81b6-411a-87a8-f85a24bda358478e7b19-524c-4c15-8dea-5fc2ce50f76d2017-01-13T16:47:422017-01-13T16:47:420ed5da14-b028-496c-8fc3-0bf81c5c1b30762e99a9-fa25-4a08-b589-658298e90b752017-01-13T15:43:412017-01-13T15:43:41762e99a9-fa25-4a08-b589-658298e90b75ce8b92dd-81b6-411a-87a8-f85a24bda3582017-01-13T15:45:082017-01-13T15:45:0812fbf2ac-fbac-467e-aa9f-f8e8007e5a3e762e99a9-fa25-4a08-b589-658298e90b752017-01-30T12:20:532017-01-30T12:20:530ed5da14-b028-496c-8fc3-0bf81c5c1b30a33dd959-8edd-417a-a5eb-3b1b59f985b62017-01-30T13:25:472017-01-30T13:25:475-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase5-HTT leading to population increase<p>Kellie Fay</p>
Under Development: Contributions and Comments WelcomeUnder Development1.29<p>Increased serotonergic activity resulting from the inhibition of the 5-hydroxytryptamin transporter (5-HTT; SERT; serotonin reuptake transporter) may result in increased population levels of certain mollusks, specifically invasive mussels. Gamete maturation and release are under serotonergic control and several mussel species have been reported to release viable gametes (both sperm and oocytes)upon exposure to serotonin or 5-HTT inhibitors, which increase serotonergic signalling. Given the critically low population levels of many Unionid species and the difficulty in managing several invasive (Dreissenid; e.g., zebra mussel) species, increased reproductive success of these invasive species may result in adverse outcomes at an ecosystem level.</p>
<p>This AOP was developed, initially, as a case study in developing an AOP for species with known or suscpected chemical exposures, in "Practical approaches to adverse outcome pathway (AOP) development and weight of evidence evaluation as illustrated by ecotoxicological case studies" by Fay et al. 2017.</p>
adjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot Specifiednon-adjacentNot SpecifiedNot Specifiednon-adjacentNot SpecifiedNot SpecifiedLowLowLowLowLowLow<p>This aop should be considered highly putative. SSRI effects in mussels have been fairly well documented as a method to increase reproduction in aquaculture settings, but the implications on natural population and potential ecosystem effects are unknown.</p>
<p>Bivalve populations which employ a broadcast spawning strategy for reproduction appear to be susceptible, including several 'invasive' species: zebra mussels, dark false mussels, and mediterranean mussels. Several species of clams and scallops also release viable gametes upon exposure to serotonin reuptake inhibitors or serotonin.</p>
<p> </p>
<p><strong>Biological plausibility:</strong> Biological plausibility refers to the structural or funtional relationships between the key events based on our understanding of 'normal biology'. Nerves immunoreactive to serotonin have been identified in the CNS and gonads of scallops and clams (e.g., Natsutani and Nomura, 1986; Masseau et al., 2002; Siniscalchi et al., 2004). Serotonin-reactive sites are also present on the surfaces of bivalve oocytes and serotonin controls germinal vesicle breakdown and, in at least some species, the progression from prophase to metaphase I (Hirai et al., 1994; Fong et al., 1994; Alvarado-Alvarez et al.,1996). Thus, the link between antagonising the serotonin reuptake transporter, which results in longer residence time of serotonin in synaptic junctions and increased serotonerigic signalling, and increased spawning and reproductive success is highly plausible.</p>
<p><strong>Dose-response concordance: </strong>While there are abundant studies in many species of bivalves indicating exposure to various serotonin reuptake inhibitors or to serotonin results in spawning in both males and females, there are not many direct comparisons available of the concentrations required to trigger upstream events vs concentrations required to trigger downstream events.</p>
<p> </p>
<p>Exposure effects are not only concentration-dependent, but also season-dependent (see Ram et al., 1993). Spawning in males appears to be more sensitive to increased serotonin than in females, at least in fingernail clams, surf clams, dark false mussels and zebra mussles (see table and references).</p>
<p>The reproductive sensitivity of many bivalves has been well-sutdied. For commercially-important species, some aquaculture facilities employ fluoxetine or other SSRIs to promote reproduction. Potential future applications of this AOP may involve pharmacological control of invasive species.</p>
Not SpecifiedNot Specified2016-11-29T18:41:172023-04-29T13:02:14