Systemic serotonin sulfate in opisthobranch mollusks

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a ubiquitous modulatory neurotransmitter with roles as a neurohormone and neurotransmitter. However, few studies have been performed characterizing this molecule and its related metabolites in circulating fluids. Here, we demonstrate native 5-HT sulfate, but much lower levels of 5-HT, in hemolymph of the marine mollusk Pleurobranchaea californica. The metabolite 5-HT sulfate forms from 5-HT uptake and metabolism in central ganglia of Aplysia californica and in the visceral nerve and eye of Pleurobranchaea, but not in hemolymph itself. In addition, 5-hydroxyindole acetic acid (5-HIAA), while not detected in hemolymph, forms in higher quantities than does 5-HT sulfate in the eye and visceral nerve, and c-glu-5-HT is also observed in this area but never in hemolymph. As systemic 5-HT sulfate appears not to originate from the optic region or from systemic 5-HT, 5-HT sulfate likely derives from the nervous system. Circulating 5-HT sulfate is at least 10-fold higher during the light portion of a 12 : 12-h light/dark cycle than during the dark portion (p < 0.0007), but there is no obvious trend for free systemic tryptophan (Trp) (p > 0.3) in Pleurobranchaea. 5-HT in mollusks is associated with general arousal state; thus, diurnal systemic changes in a 5-HT catabolite may reflect a regulatory role for indole catabolism in behavioral rhythms. Keywords: capillary electrophoresis, hemolymph, marine mollusk, serotonin, sulfation. Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic amine responsible for a variety of tasks in the nervous system. For instance, 5-HT is implicated in learning and memory in the central nervous system (CNS) and emesis and peristaltic reflex in the enteric nervous system (ENS) (Bartsch et al. 2000;Buhot et al. 2000;Endo et al. 2000). Several organs serve as targets for 5-HT, but the fate of 5-HT in target tissues, let alone the physiological effects of the resulting metabolites, has not been fully ascertained. Knowledge of the products of transformed 5-HT, as well as their distribution patterns, will assist in illuminating the processes leading to impaired neurotransmission and eventually aid in designing compounds that could potentially inhibit disease in neural and surrounding tissues.Marine mollusks present an excellent model for the study of the nervous system because of their large cell somata and well-characterized neural networks. In gastropod mollusks, 5-HT is involved in many neurophysiological processes, including sensitization and facilitation of withdrawal reflexes (Hawkins et al. 1993), feeding behavior (Gillette and Davis 1977) and locomotion (McPherson and Blankenship 1991). However, 5-HT-related metabolites have received considerably less attention.Our laboratory recently demonstrated that 5-HT metabolism in Aplysia californica involves sulfation and c-glutamylation with trace amounts of monoamine oxidase activity present in the form of 5-hydroxyindole acetic acid (5-HIAA) (Stuart et al. 2003). In particular, 5-HT sulfate is present ...

Application of 5-HT-SO4 in Biomarker Research

“…Also, indings in sea molluscs indicate that metabolism of serotonin with further formation of 5-HT-SO 4 depends upon the location of release. Thus, haemolymph 5-HT-SO 4 most probably originates from the nervous system [7,8]. There is also no doubt about the entrance of ingested 5-HTP into CNS [21].…”

“…Later, a similar compound was found in human urine, cerebrospinal liquor and platelets [4][5][6]. During recent years, some research was done with marine molluscs determining 5-HT-SO 4 in their nervous system [7,8]. Findings showed that the serotonin metabolite 5-HT-SO 4 forms from 5-HT uptake and metabolism in central ganglia and other structures of nervous system but not in haemolymph itself.…”

“…Some research was conducted with marine molluscs determining 5-HT-O-SO 4 in their nervous system [7,8].…”

The serotonin-O-sulfate as a potential plasma surrogate biomarker

“…Thus it was concluded that 5-HT-SO4 detected in hemolymph is most probably originating from the nervous system [17,18] . This suggests us that given compound could emphasizes intensity of serotonin metabolism in the nervous system.…”

“…Findings showed that the 5-HT-SO4 forms from 5-HT uptake and metabolism in central ganglia and other structures of nervous system, but not in hemolymph per se. The scheme of metabolism according to the Stuart et al is showed below [17,18] . Serotonin can also be glucuronidated by action of the enzyme uridine diphosphate glucuronyltrans-ferase.…”