Abstract
In the Gulf toadfish (Opsanus beta), the serotonin (5-HT) transporter (SERT) is highly expressed in the heart, and the heart and gill both demonstrate the capacity for SERT-mediated uptake of 5-HT from the circulation. Because 5-HT is a potent vasoconstrictor in fish, we hypothesized that hypoxia exposure may increase 5-HT uptake by these tissues—and increase excretion of 5-HT—to prevent branchial vasoconstriction that would hamper gas exchange. Spot sampling of blood, bile, and urine revealed that fish exposed to chronic hypoxia (1.83 ± 0.12 mg·L−1 O2 for 24–26 h) had 41% lower plasma 5-HT in the ventral aorta (immediately following the heart) than in the hepatic vein (immediately before the heart), suggesting enhanced cardiac 5-HT uptake during hypoxia. 5-HT concentrations in the bile were greater than those in the urine, but there were no effects of acute (1.31 ± 0.06 mg·L−1 O2 for 25 min) or chronic hypoxia on 5-HT levels in these fluids. In 5-HT radiotracer experiments, the presence of tracer in the bile decreased upon hypoxia exposure, but, surprisingly, neither acute nor chronic hypoxia-induced changes in [3H]5-HT uptake in the heart, gill, or other tissues. Given the likely impact of the hypoxia exposure on metabolic rate, future studies should examine the effects of a milder hypoxia exposure on 5-HT uptake into these tissues and the role of 5-HT degradation.
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References
Al Ahmad A, Gassmann M, Ogunshola OO (2012) Involvement of oxidative stress in hypoxia-induced blood-brain barrier breakdown. Microvasc Res 84:222–225. https://doi.org/10.1016/j.mvr.2012.05.008
Al Ahmad A, Gassmann M, Ogunshola OO (2009) Maintaining blood-brain barrier integrity: pericytes perform better than astrocytes during prolonged oxygen deprivation. J Cell Physiol 218:612–622. https://doi.org/10.1002/jcp.21638
Amador MHB, McDonald MD (2018a) Molecular and functional characterization of the Gulf toadfish serotonin transporter SLC6A4. J Exp Biol 221:jeb.170928. https://doi.org/10.1242/jeb.170928
Amador MHB, McDonald MD (2018b) The serotonin transporter and nonselective transporters are involved in peripheral serotonin uptake in the Gulf toadfish, Opsanus beta. Am J Physiol 315:R1154–R1166. https://doi.org/10.1152/ajpregu.00137.2018
Amador MHB, Schauer KL, McDonald MD (2018) Does fluoxetine exposure affect hypoxia tolerance in the Gulf toadfish, Opsanus beta? Aquat Toxicol 199:55–64. https://doi.org/10.1016/j.aquatox.2018.03.023
Anderson C, Campbell G (1988) Immunohistochemical study of 5-HT-containing neurons in the teleost intestine: relationship to the presence of enterochromaffin cells. Cell Tissue Res 254:553–559. https://doi.org/10.1007/BF00226505
Anderson CR, Campbell G, Payne M (1989) Metabolic origins of 5-hydroxytryptamine in enteric neurons in a teleostean fish (Platycephalus bassensis), a toad (Bufo marinus) and the guinea-pig. Comp Biochem Physiol 92C:253–258. https://doi.org/10.1016/0742-8413(89)90049-2
Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, Koldzic-Zivanovic N, Jeske NA, Koek W, Toney GM, Daws LC (2008) Organic cation transporter 3: keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci USA 105:18976–18981. https://doi.org/10.1073/pnas.0800466105
Bailly Y, Dunel-Erb S, Geffard M, Laurent P (1989) The vascular and epithelial serotonergic innervation of the actinopterygian gill filament with special reference to the trout, Salmo gairdneri. Cell Tissue Res 258:349–363. https://doi.org/10.1007/BF00239455
Bauer AT, Bürgers HF, Rabie T, Marti HH (2010) Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement. J Cereb Blood Flow Metab 30:837–848. https://doi.org/10.1038/jcbfm.2009.248
Brooks BW, Chambliss CK, Stanley JK, Ramirez A, Banks KE, Johnson RD, Lewis RJ (2005) Determination of select antidepressants in fish from an effluent-dominated stream. Environ Toxicol Chem 24:464–469. https://doi.org/10.1897/04-081R.1
Caamaño-Tubío RI, Pérez J, Ferreiro S, Aldegunde M (2007) Peripheral serotonin dynamics in the rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol 145C:245–255. https://doi.org/10.1016/j.cbpc.2006.12.017
Cartolano MC, Amador MHB, Tzaneva V, Milsom WK, McDonald MD (2017) Extrinsic nerves are not involved in branchial 5-HT dynamics or pulsatile urea excretion in Gulf toadfish, Opsanus beta. Comp Biochem Physiol 214A:58–65. https://doi.org/10.1016/j.cbpa.2017.08.009
Clotfelter ED, O’Hare EP, McNitt MM, Carpenter RE, Summers CH (2007) Serotonin decreases aggression via 5-HT1A receptors in the flighting fish Betta splendens. Pharmacol Biochem Behav 87:222–231
Cooper BR, Hester TJ, Maxwell RA (1980) Behavioral and biochemical effects of the antidepressant bupropion (Wellbutrin): evidence for selective blockade of dopamine uptake in vivo. J Pharmacol Exp Ther 215:127–134
Davis JN, Carlsson A (1973) The effect of hypoxia on monoamine synthesis, levels and metabolism in rat brain. J Neurochem 21:783–790. https://doi.org/10.1111/j.1471-4159.1973.tb07522.x
De Pedro N, Pinillos ML, Valenciano AI, Alonso-Bedate M, Delgado MJ (1998) Inhibitory effect of serotonin on feeding behavior in goldfish: involvement of CRF. Peptides 19:505–511
Dunel-Erb S, Bailly Y, Laurent P (1982) Neuroepithelial cells in fish gill primary lamellae. J Appl Physiol 53:1342–1353
Edwards D, Hall TR, Brown JA (1986) The characteristics and distribution of monoamine oxidase (MAO) activity in different tissues of the rainbow trout, Salmo gairdneri. Comp Biochem Physiol 84C:73–77. https://doi.org/10.1016/0742-8413(86)90167-2
Focazio MJ, Kolpin DW, Barnes KK, Furlong ET, Meyer MT, Zaugg SD, Barber LB, Thurman ME (2008) A national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United States - II) untreated drinking water sources. Sci Total Environ 402:201–216. https://doi.org/10.1016/j.scitotenv.2008.02.021
Fritsche R, Thomas S, Perry SF (1992) Effects of serotonin on circulation and respiration in the rainbow trout Oncorhynchus mykiss. J Exp Biol 73:59–73
Gaweska H, Fitzpatrick PF (2011) Structures and mechanism of the monoamine oxidase family. Biomol Concepts 2:365–377. https://doi.org/10.1515/BMC.2011.030
Gaworecki KM, Klaine SJ (2008) Behavioral and biochemical responses of hybrid striped bass during and after fluoxetine exposure. Aquat Toxicol 88:207–213
Gutierrez A, Saracibar G, Casis L, Echevarria E, Rodriguez VM, Macarulla MT, Abecia LC, Portillo MP (2002) Effects of fluoxetine administration on neuropeptide y and orexins in obese zucker rat hypothalamus. Obes Res 10:532–540. https://doi.org/10.1038/oby.2002.72
Hird CM, Urbina MA, Lewis CN, Snape JR, Galloway TS (2016) Fluoxetine exhibits pharmacological effects and trait-based sensitivity in a marine worm. Environ Sci Technol 50:8344–8352. https://doi.org/10.1021/acs.est.6b03233
Höglund E, Balm PHM, Winberg S (2002) Stimulatory and inhibitory effects of 5-HT1A receptors on adrenocorticotropic hormone and cortisol secretion in an teleost fish, the Arctic charr (Salvelinus alpinus). Neurosci Lett 324:193–196
Hyun SW, Jung YS (2014) Hypoxia induces FoxO3a-mediated dysfunction of blood-brain barrier. Biochem Biophys Res Commun 450:1638–1642. https://doi.org/10.1016/j.bbrc.2014.07.055
Janvier J, Peyraud-Waïtzenegger M, Soulier P (1996) Effects of serotonin on the cardio-circulatory system of the European eel (Anguilla anguilla) in vivo. J Comp Physiol 166B:131–137. https://doi.org/10.1007/BF00301176
Khan IA, Thomas P (1996) Disruption of neuroendocrine function in Atlantic croaker exposed to Aroclor 1254. Mar Environ Res 42:145–149
Kiliaan AJ, Dekker K, Groot JA (1989) Serotonergic neurons in the intestine of two teleosts, Carassius auratus and Oreochromis mossambicus, and the effect of serotonin on transepithelial ion-selectivity and muscle tension. Neuroscience 31:817–824
Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999–2000: a national reconnaissance. Environ Sci Technol 36:1202–1211. https://doi.org/10.1021/es011055j
Kristensen AS, Andersen J, Jorgensen TN, Sorensen L, Eriksen J, Loland CJ, Stromgaard K, Gether U (2011) SLC6 neurotransmitter transporters: structure, function, and regulation. Pharmacol Rev 63:585–640. https://doi.org/10.1124/pr.108.000869
Kupiec TP (2004) Quality-control analytical methods: high-performance liquid chromatography. Int J Pharm Compd 8:223–227
Laurent P (1984) Gill internal morphology. In: Hoar WS, Randall DJ (eds.) Fish Physiol, Vol. 10A. New York: Academic Press. pp 73–183
Lim JE, Porteus CS, Bernier NJ (2013) Serotonin directly stimulates cortisol secretion from the interrenals in goldfish. Gen Comp Endocrinol 192:246–255
Liu YL, Connoley IP, Harrison J, Heal DJ, Stock MJ (2002) Comparison of the thermogenic and hypophagic effects of sibutramine’s metabolite 2 and other monoamine reuptake inhibitors. Eur J Pharmacol 452:49–56. https://doi.org/10.1016/S0014-2999(02)02226-4
Liu YL, Connoley IP, Heal DJ, Stock MJ (2004) Pharmacological characterisation of the thermogenic effect of bupropion. Eur J Pharmacol 498:219–225. https://doi.org/10.1016/j.ejphar.2004.07.004
Marcinkiewcz CA, Devine DP (2015) Modulation of OCT3 expression by stress, and antidepressant-like activity of decynium-22 in an animal model of depression. Pharmacol Biochem Behav 131:33–41. https://doi.org/10.1016/j.pbb.2015.01.004
Mawe GM, Hoffman JM (2013) Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol 10:473–486. https://doi.org/10.1038/nrgastro.2013.105
McDonald MD (2017) An AOP analysis of selective serotonin reuptake inhibitors (SSRIs) for fish. Comp Physiol Biochem 197C:19–31. https://doi.org/10.1016/j.cbpc.2017.03.007
McDonald MD, Walsh PJ (2004) Dogmas and controversies in the handling of nitrogenous wastes: 5-HT2-like receptors are involved in triggering pulsatile urea excretion in the gulf toadfish, Opsanus beta. J Exp Biol 207:2003–2010. https://doi.org/10.1242/jeb.00957
McDonald MD, Gilmour KM, Walsh PJ, Perry SF (2010) Cardiovascular and respiratory reflexes of the gulf toadfish (Opsanus beta) during acute hypoxia. Respir Physiol Neurobiol 170:59–66. https://doi.org/10.1016/j.resp.2009.12.012
McDonald MD, Wood CM, Walsh PJ (2012) 5-hydroxytryptamine initiates pulsatile urea excretion from perfused gills of the Gulf toadfish (Opsanus beta). Comp Biochem Physiol 163A:30–37. https://doi.org/10.1016/j.cbpa.2012.04.027
McIsaac WM, Page IH (1959) The metabolism of serotonin (5-hydroxytryptamine). J Biol Chem 234:858–864
Medeiros LR, Cartolano MC, McDonald MD (2014) Crowding stress inhibits serotonin 1A receptor-mediated increases in corticotropin-releasing factor mRNA expression and adrenocorticotopin hormone secretion in the Gulf toadfish. J Comp Physiol 184B:259–271
Mennigen JA, Martyniuk CJ, Crump K, Xiong HL, Zhao E, Popesku J, Anisman H, Cossins AR, Xia XH, Trudeau VL (2008) Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus). Physiol Genomics 35:273–282
Mennigen JA, Lado WE, Zamoraa JM, Duarte-Guterman P, Langlois VS, Metcalfe CD, Chang JP, Moon TW, Trudeau VL (2010) Waterborne fluoxetine disrupts the reproductive axis in sexually mature male goldfish, Carassius auratus. Aquat Toxicol 100:354–364. https://doi.org/10.1016/j.aquatox.2010.08.016
Morando MB, Medeiros LR, McDonald MD (2009) Fluoxetine treatment affects nitrogen waste excretion and osmoregulation in a marine teleost fish. Aquat Toxicol 95:164–171. https://doi.org/10.1016/j.aquatox.2009.10.015
Nagai T, Hamada M, Kai N, Tanoue Y, Nagayama F (1997) Organ distribution of tryptophan hydroxylase activity in several fish. Fish Sci 63:652–653
Olson KR (1998) Hormone metabolism by the fish gill. Comp Biochem Physiol 119:55–65. https://doi.org/10.1016/S1095-6433(97)00406-6
Olson EB, Vidruk EH, McCrimmon DR, Dempsey JA (1983) Monoamine neurotransmitter metabolism during acclimatization to hypoxia in rats. Respir Physiol 54:79–96. https://doi.org/10.1016/0034-5687(83)90115-9
Olsson C, Holmberg A, Holmgren S (2008) Development of enteric and vagal innervation of the zebrafish (Danio rerio) gut. J Comp Neurol 508:756–770. https://doi.org/10.1002/cne.21705
Ortega VA, Lovejoy DA, Bernier NJ (2013) Appetite-suppressing effects and interactions of centrally administered corticotropin-releasing factor, urotensin I and serotonin in rainbow trout (Oncorhynchus mykiss). Front Neurosci 7:196
Panlilio JM, Marin S, Lobl MB, McDonald MD (2016) Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response. Sci Rep 6:1–12. https://doi.org/10.1038/srep31148
Pelster B, Schwerte T (2012) The paracrine role of 5-HT in the control of gill blood flow. Respir Physiol Neurobiol 184:340–346. https://doi.org/10.1016/j.resp.2012.05.014
Perez Maceira JJ, Mancebo MJ, Aldegunde M (2014) The involvement of 5-HT-like receptors in the regulation of food intake in rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol CBP 161C:1–6
Prasad P, Ogawa S, Parhar IS (2015) Role of serotonin in fish reproduction. Front Neurosci 9:195
Sebire M, Davis JE, Hatfield R, Winberg S, Katsiadaki I (2015) Prozac affects stickleback nest quality without altering androgen, spiggin or aggression levels during a 21-day breeding test. Aquat Toxicol 168:78–89
Senthilkumaran B, Sudhakumari CC, Mamta SK, Raghuveer K, Swapna I, Murugananthkumar R (2015) “Brain sex differentiation” in teleosts: emerging concepts with potential biomarkers. Gen Comp Endocrinol 220:33–40
Slánský J, Kadlec O, Sevcik J, Masek K (1996) Further evidence on the interaction of muramyl dipeptide with the serotonergic system. Int J Immunopharmacol 18:23–29
Smith LS (1966) Blood volumes of three salmonids. J Fish Res Board Can 23:1439–1446
Stinson J, Murphy C, Tomkin G (1992) An assessment of the thermogenic effects of fluoxetine in obese subjects. Int J Obes Relat Metab Disord 16:391–395
Stoyek MR, Jonz MG, Smith FM, Croll RP (2017) Distribution and chronotropic effects of serotonin in the zebrafish heart. Auton Neurosci Basic Clin 206:43–50. https://doi.org/10.1016/j.autneu.2017.07.004
Sundin L, Nilsson GE (2000) Branchial and circulatory responses to serotonin and rapid ambient water acidification in rainbow trout. J Exp Zool 287:113–119. https://doi.org/10.1002/1097-010X(20000701)287:2%3c113::AID-JEZ1%3e3.0.CO;2-1
Sundin L, Nilsson GE, Block M, Löfman CO (1995) Control of gill filament blood flow by serotonin in the rainbow trout, Oncorhynchus mykiss. Am J Physiol 268:R1224–R1229
Sundin L, Davison W, Forster M, Axelsson M (1998) A role of 5-HT2 receptors in the gill vasculature of the Antarctic fish Pagothenia borchgrevinki. J Exp Biol 201:2129–2138
Sweet LE, Bisesi JH Jr, Lei ENY, Lam MHW, Klaine SJ (2016) The effects of bupropion on hybrid striped bass brain chemistry and predatory behavior. Environ Toxicol Chem 35:2058–2065. https://doi.org/10.1002/etc.3350
Velarde E, Delgado MJ, Alonso-Gomez AL (2010) Serotonin-induced contraction in isolated intestine from a teleost fish (Carassius auratus): characterization and interactions with melatonin. Neurogastroenterol Motil 22:e364-373
Vasskog T, Anderssen T, Pedersen-Bjergaard S, Kallenborn R, Jensen E (2008) Occurrence of selective serotonin reuptake inhibitors in sewage and receiving waters at Spitsbergen and in Norway. J Chromatogr A 1185:194–205. https://doi.org/10.1016/j.chroma.2008.01.063
Wood C, Hopkins T, Walsh P (1997) Pulsatile urea excretion in the toadfish (Opsanus beta) is due to a pulsatile excretion mechanism, not a pulsatile production mechanism. J Exp Biol 200:1039–1046
Acknowledgements
We would like to thank Tony’s Live Bait, Miami, FL, for their continued supply of Gulf toadfish.
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This study was funded by a National Science Foundation grant (IOS-1754550) to MD McDonald.
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Molly HB Amador. The first draft of the manuscript was written by Molly HB Amador, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Amador, M.H.B., McDonald, M.D. Is serotonin uptake by peripheral tissues sensitive to hypoxia exposure?. Fish Physiol Biochem 48, 617–630 (2022). https://doi.org/10.1007/s10695-022-01083-3
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DOI: https://doi.org/10.1007/s10695-022-01083-3