The serotonin transporter and nonselective transporters are involved in peripheral serotonin uptake in the Gulf toadfish,Opsanus beta

Abstract

In mammals, circulating serotonin [5-hydroxytryptamine (5-HT)] is sequestered by platelets via the 5-HT transporter (SERT) to prevent unintended signaling by this potent signaling molecule. Teleost fish appear to lack a similar circulating storage pool, although the diverse effects of 5-HT in teleosts likely necessitate an alternative method of tight regulation, such as uptake by peripheral tissues. Here, a 5-HT radiotracer was used to explore the 5-HT uptake capacity of peripheral tissues in the Gulf toadfish, Opsanus beta, and to elucidate the primary excretion routes of 5-HT and its metabolites. Pharmacological inhibition of SERT and other transporters enabled assessment of the SERT dependence of peripheral 5-HT uptake and excretion. The results indicated a rapid and substantial uptake of 5-HT by the heart atrium, heart ventricle, and gill that was at least partly SERT dependent. The results also supported the presence of a partial blood-brain barrier that prevented rapid changes in brain 5-HT content despite fluctuating plasma 5-HT concentrations. The renal pathway appeared to be the dominant excretory route for 5-HT and its metabolites over shorter time frames (up to ~30 min), but hepatic excretion was substantial over several hours. SERT inhibition ultimately reduced the excretion of 5-HT and its metabolites by urinary, biliary, and/or intestinal pathways. In addition, branchial excretion of 5-HT and its metabolites could not be ruled out. In summary, this study reveals that the toadfish heart and gill play active roles in regulating circulating 5-HT and yields important insights into the control of peripheral 5-HT in this teleost fish.

Cardiovascular serotonergic system: Evolution, receptors, transporter, and function

“…Mammalian SERT is composed of 630 amino acids with 12 hydrophobic transmembrane spanning regions and both the amino and carboxyl termini are on the cytoplasmic side of the membrane. SERT/NSS transporter family members, like serotonin have been evolutionarily conserved for millions of years and are present in bacteria, insects, invertebrates, and all vertebrates (Amador & McDonald, 2018b; Corey et al, 1994; Demchyshyn et al, 1994). The Drosophila melanogaster transporter, dSERT, has 622 amino acids, 12 trans‐membrane regions, has a pharmacological profile and rank order of potency like the mammalian SERT, shares 104 conserved amino acid residues with all other transporters and has approximately 50% sequence identity with mammalian SERT (Corey et al, 1994; Demchyshyn et al, 1994).…”

“…It is interesting that all teleosts studied express SERT mRNA in every tissue examined with the highest concentration found in the cerebellum and the heart. No teleost tissue, except neuroepithelial cells in the gill (as detected in the toadfish) stored serotonin in vesicles (Amador & McDonald, 2018b). Unlike mammalian platelets, fish thrombocytes, presumed precursor of platelets (Soslau, 2020), do not store serotonin in granules.…”

“…Teleost serotonin in the extracellular milieu evokes the same/similar physiological responses in the cardiovascular system as observed in mammalian systems with SERT likely being an important regulator of extracellular levels of the hormone. However, toadfish renal and hepatic pathways exist to clear most of the extracellular serotonin and its metabolites (Amador & McDonald, 2018b).…”

Depressive Symptoms are Associated with low Serotonin Levels in Plasma but are not 5–HTTLPR Genotype Dependent in Older Adults

“…The serotonin transporter (SERT) is a protein that is found in the platelet plasma membrane. It regulates circulating serotonin levels by inducing the accumulation of serotonin within platelets (Amador & McDonald, 2018). The SERT protein expressed in platelets is identical to that found in neurons, displaying similar structural and functional properties in both tissues (Mammadova-Bach et al, 2018).…”