Neurochemistry and neuropharmacology of emesis — the role of serotonin

Endô, Tôru; Minami, Masaru; Hirafuji, Masahiko; Ogawa, Takashi; Akita, Kumi; Nemoto, M.; Saito, Hiroshi; Yoshioka, Mitsuhiro; Parvez, S.

doi:10.1016/s0300-483x(00)00314-0

Cited by 85 publications

(79 citation statements)

References 62 publications

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“…Input from the AP to the NTS, however, was also apparently inhibited by granisetron. These fi ndings suggest that granisetron blocks input to the NTS in addition to acting on 5-HT 3 receptors on the peripheral terminals of the abdominal afferent vagal fi bers (15,16).…”

Section: Discussionmentioning

confidence: 99%

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

et al. 2004

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Cancer chemotherapy-induced nausea and vomiting have been demonstrated to involve humoral as well as neuronal mechanisms. A leading role of serotonin (5-hydroxytryptamine, 5-HT) in these mechanisms is supported by inhibition of the emesis by 5-HT 3 receptor antagonists. We compared the effects of granisetron, a selective 5-HT 3 receptor antagonist, and vagotomy on c-fos mRNA expression in the nucleus of the solitary tract (NTS) and the area postrema (AP) of the rat caudal brainstem by means of in situ hybridization. The expression of c-fos mRNA in the NTS and AP was signifi cantly elevated 2 h after cisplatin administration. The induction of c-fos expression by cisplatin in the NTS was signifi cantly inhibited by pretreatment with granisetron. In contrast, the c-fos expression in the AP did not differ between the cisplatin group and the granisetron-treated cisplatin group. The degree of the induction of c-fos mRNA expression in both the AP and NTS was similar between the vagotomy and sham operation groups. Our results suggest that the expression of c-fos mRNA in the NTS may be specifi cally controlled by 5-HT 3 receptors and that nonspecifi c humoral factors, such as modulation of transcriptional activity, play an important role in c-fos expression in the AP after vagotomy.Neuronal sites and signal substances involved in cancer chemotherapy-induced nausea and vomiting have been identifi ed neurochemically (20). Serotonin type 3 receptor (5-HT 3 receptor) antagonists protect against emesis in experimental animal models as well as in cisplatin-treated patients with cancer (35). Autoradiographic studies of 5-HT in the central nervous system showed that binding sites with the strongest affi nity for 5-HT 3 receptors are located in the nucleus of the solitary tract (NTS) and the area postrema (AP) of the caudal brainstem (33).However, considerable evidence supports the hypothesis that cytotoxic drug-induced emesis is mediated by local 5-HT release in the intestinal wall (4,14,15,27,28). 5-HT has a potent depolarizing action on the vagal afferent nerve (18,34). It has been proposed that anticancer drugs cause 5-HT release from enterochromaffin (EC) cells to activate the 5-HT 3 receptors on the afferent vagal nerve fi bers (1,26). These afferent fi bers may project to the dorsal vagal complex, which also expresses 5-HT 3 receptors on its central terminals (20,33). The vomiting center receives input from the afferent vagal fi bers to evoke an emetic refl ex (1,20). The vagus is the major nerve involved in the detection of emetic stimuli, and the abdominal vagus contains approximately 80-90% of the afferent fi bers (3). Electrical

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Section: Discussionmentioning

confidence: 99%

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

et al. 2004

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“…Their role in that is particularly evident from the fact that 5-HT 3 receptor antagonists are very effective antiemetic drugs (Costall and Naylor, 2004). Regulation of intestinal motility, nausea and vomiting is probably mediated by 5-HT 3 receptors expressed in the gut (Endo et al, 2000), but the 5-HT 3 receptors are also present in the central nervous system, specifically in the hippocampus, the amygdala, the nucleus tractus solitarii, the area postrema, and the spinal cord (Laporte et al, 1992). The exact role of the 5-HT 3 receptors in the central nervous system is still not fully understood (Costall and Naylor, 2004;Van Hooft and Yakel, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…The exact role of the 5-HT 3 receptors in the central nervous system is still not fully understood (Costall and Naylor, 2004;Van Hooft and Yakel, 2003). It is suggested that the brain 5-HT 3 receptors are also involved in the regulation of nausea and vomiting (Endo et al, 2000), but they appear to be involved in regulation of mental functions as well and may play a role in various psychiatric disorders (Costall and Naylor, 2004). The application of 5-HT 3 receptor antagonists in animal models has shown psychotropic effects like anxiolysis and improvement of cognitive functions.…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine

Tzvetkov¹,

Meineke²,

Oetjen

et al. 2007

Gene

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“…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.…”

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confidence: 99%

Systemic serotonin sulfate in opisthobranch mollusks

Stuart¹,

Ebaugh²,

Copes³

et al. 2004

Journal of Neurochemistry

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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 ...

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Neurochemistry and neuropharmacology of emesis — the role of serotonin

Cited by 85 publications

References 62 publications

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine

Systemic serotonin sulfate in opisthobranch mollusks

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