The enteric neural receptor for 5-hydroxytryptamine

Gershon, Michael D.; Takaki, Miyako; Tamir, Hadassah; Branchek, Theresa A.

doi:10.1007/bf01970002

Cited by 46 publications

(9 citation statements)

References 33 publications

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“…(Wood & Mayer, 1979). In many respects the pharmacology of these effects is remarkably similar to that observed in this study (Gershon, Takaki, Tamir & Branchek, 1985;Surprenant & Crist, 1986).…”

Section: Discussionsupporting

confidence: 86%

Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro.

Andrade

Nicoll

1987

The Journal of Physiology

526

300

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SUMMARY1. The actions of serotonin (5-HT) on pyramidal cells of the CAI region of the rat hippocampus were characterized using intracellular recording in in vitro brain slices.2. 5-HT typically evokes a biphasic response consisting of a hyperpolarization which is followed by a longer-lasting depolarization. These effects on membrane potential are accompanied by a decrease in the calcium-activated after-hyperpolarization (a.h.p).3. Detailed analysis using 5-HT antagonists and agonists indicates that the hyperpolarization is mediated by a 5-HTlA receptor. Spiperone is the most effective antagonist of the response and the selective 5-HTlA agonist, 8-OHDPAT, behaves as a partial agonist at this receptor. In agreement with the distribution of 5-HTlA binding sites, responses to 5-HT were most prominent in the stratum radiatum.4. The hyperpolarizing response is associated with a decrease in input resistance, is blocked by extracellular barium and intracellular caesium, is unaffected by the chloride gradient, and its reversal potential shifts with the extracellular concentration of potassium as predicted for a response mediated by a selective increase in potassium permeability.5. The depolarizing response and reduction in the a.h.p. could be studied in isolation by blocking the hyperpolarizing response with either pertussis toxin or spiperone. The pharmacology of these responses did not correspond to that of any of the 5-HT binding sites reported in C.N.S. tissue. Although the depolarization and blockade of the a.h.p. have the same time course it is unclear if they are mediated by the same or different receptors.6. The depolarization most likely results from a decrease in resting potassium conductance. However, neither a blockade of the M current nor the a.h.p. current can account for the depolarization.7. Blockade of phosphodiesterase activity by 3-isobutyl-l-methylxanthine (IBMX) did not enhance the depressant action of 5-HT on the a.h.p., making it unlikely that this action is mediated by cyclic AMP.

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Section: Discussionsupporting

confidence: 86%

Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro.

Andrade

Nicoll

1987

The Journal of Physiology

526

300

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“…4) receptors (23) Electrophysiological observations made in this and other studies (12,13) In contrast, 2-methyl-5-HT, which is more potent than 5-or 6-OHIP in eliciting an effect that resembles the fast response to 5-HT, mimics (or desensitizes) the slow response only at relatively high concentrations of the compound. The affinity of indolic compounds for the 5-HTP-DP-sensitive receptor requires hydroxylation of the indole ring; thus, indalpine, like tryptamine and 5-methoxytryptamine (12,13,20,21), does not act at this site. Actions of these compounds, reported to be 5-HT-like from pharmacological studies of muscle contraction, may be due to effects on ICS 205-930-sensitive receptors, to other receptors, or to other types of action, such as the release of 5-HT by tryptamine (13).…”

Section: Resultsmentioning

confidence: 99%

“…The D receptors are located on smooth muscle, whereas the M receptors are entirely neural. It seems likely that D receptors are similar to 5-HT2 receptors of the central nervous system (19); however, the category of M receptor seems unique to the periphery and has only recently begun to be characterized (18,20,21). Because this class of receptor appears to be responsible for mediating the painful effects of 5-HT in humans, considerable interest has been focused on M receptors (18,22 Additional compounds, besides dipeptides of 5-hydroxytryptophan, have also been reported to be antagonists of 5-HT at M receptors.…”

mentioning

confidence: 99%

Peripheral neural serotonin receptors: identification and characterization with specific antagonists and agonists.

Mawe¹,

Branchek²,

Gershon³

1986

Proc. Natl. Acad. Sci. U.S.A.

170

103

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Serotonin (5-hydroxytryptamine, 5-HT) has been shown to be a neurotransmitter in the enteric nervous system (ENS). Although 5-HT is a mediator of slow excitatory postsynaptic potentials evoked by stimulation of interganglionic connectives, the precise role it plays in the physiology of the gut is unclear. Research has been hampered by an inadequate knowledge of the types of 5-HT receptor in the ENS and thus the lack of well-characterized antagonists. We now report the identification of two classes of enteric neural 5-HT receptor, the effects of activating these receptors on myenteric type II/AH neurons, and their characterization with specific agonists and antagonists. One class, which we propose to call 5-HT1p, is characterized by a high affinity for [3H]5-HT in radioligand binding assays. This class of receptor mediates a slow depolarization of myenteric type II/AH neurons associated with an increase in input resistance. Agonists at this receptor include, in addition to 5-HT (in order of potency), 5-and 6-hydroxyindalpine and 2-methyl-5-HT. 5-HTlp-mediated Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter in the enteric nervous system (ENS) (1-3). Nevertheless, its precise role in the control of gastrointestinal motility or secretion is not clear. In part, this uncertainty arises because 5-HT has many actions on the neurons, muscle, and epitheHum of the gut and it has been difficult to determine which of these are of physiological significance. The neuronal effects of 5-HT include excitation of mucosal afferent fibers to initiate the peristaltic reflex (4, 5), a presynaptic inhibition of the release of acetylcholine (AcCho) from activated myenteric axons (6), stimulation of excitatory enteric neurons to cause a net release of AcCho resulting in smooth muscle contraction, and a relaxation of the bowel secondary to the activation of nonadrenergic, noncholinergic inhibitory neurons (7). Direct application of 5-HT onto myenteric type II/AH neurons may result in a rapid depolarization of the cells associated with an increase in membrane conductance (8), a slow depolarization associated with a decreased membrane conductance (9, 10), a hyperpolarization associated with an increase in membrane conductance, or, with different time courses, all of these responses (11-13). The development of an understanding of the physiological significance of the many effects of exogenous 5-HT has been hampered by the absence, until recently, of specific antagonists of the enteric neural actions of the amine.To utilize 5-HT antagonists effectively it is necessary to characterize the types of 5-HT receptor present in the gut. Gaddum and Picarelli (14) first classified the 5-HT receptors of the bowel as "D" or "M" receptors because they found responses of the guinea pig ileum to 5-HT that could be blocked by phenoxybenzamine (dibenzyline) or morphine, respectively. Although neither of these compounds is a specific antagonist of 5-HT, the terms D and M are now well established and each denotes a distinct receptor populat...

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“…These data are in accordance with the previous in vitro electrophysiological studies showing that 5-HT inhibits coupled NaCl absorption in the small intestine and gall bladder of rabbit (10) and rat colon (6). 5-HT has also been shown to inhibit the Cl Ϫ /HCO 3 Ϫ exchange activity in villus cells and stimulate HCO 3 Ϫ secretion in crypt cells of the rabbit ileum (12). Earlier studies have also demonstrated 5-HT to increase electrogenic chloride secretion in the guinea pig ileum (9), rat ileum (8), jejunum (7), distal colon (6), and human jejunum (13).…”

Section: -Ht-induced Tyrosine Phosphorylation Of Pkc␦ In Caco-2 Cellmentioning

confidence: 97%

“…5-HT has also been shown to inhibit the NaClabsorptive process in the rabbit ileum and gall bladder (10) but has no effect in rabbit and guinea pig colon (10,11). Moreover, Sundaram et al (12) have demonstrated that 5-HT inhibits Cl Ϫ /HCO 3 Ϫ exchange activity in villus cells and stimulates HCO 3 Ϫ secretion in crypt cells of the rabbit ileum. In contrast, 5-HT appears to have no significant effect on coupled NaCl absorption in the human jejunum (13).…”

Section: -Htmentioning

confidence: 99%

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

Saksena

Gill

Tyagi

et al. 2005

Journal of Biological Chemistry

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The gastrointestinal tract is an important source of the endogenous amine, serotonin, mainly stored in the mucosal enterochromaffin cells and in the enteric nervous system (1). 5-HT1 is continuously released from the enterochromaffin cells in the intestinal mucosa into the portal circulation and the gut lumen in response to a variety of luminal stimuli such as change in pH or osmolarity and mechanical and chemical stimuli (2). 5-HT is an important neurotransmitter and intercellular messenger to modulate gastrointestinal functions (3). 5-HT has been shown to alter gastrointestinal motility (4), alter gastric acid secretion, and enhance intestinal secretions (1, 5). Most of the previous studies regarding the effects of serotonin on ion transport were mainly based on the electrophysiological data including short circuit current measurements and unidirectional fluxes. These studies showed that 5-HT stimulated electrogenic Cl Ϫ secretion and inhibited Na ϩ and Cl Ϫ absorption in the rat colon (6), jejunum (7), ileum (8), and guinea pig ileum (9). 5-HT has also been shown to inhibit the NaClabsorptive process in the rabbit ileum and gall bladder (10) but has no effect in rabbit and guinea pig colon (10, 11). Moreover, Sundaram et al. (12) have demonstrated that 5-HT inhibits Cl Ϫ /HCO 3 Ϫ exchange activity in villus cells and stimulates HCO 3 Ϫ secretion in crypt cells of the rabbit ileum. In contrast, 5-HT appears to have no significant effect on coupled NaCl absorption in the human jejunum (13).5-HT exerts its effects by binding to 5-HT receptors, which are distributed on the neuronal, muscular, and epithelial structures (14). Based on pharmacological studies and molecular cloning (15), the existence of at least seven 5-HT receptors (5-HT1-7) subdivided into 14 subtypes has been discovered. With the exception of 5-HT5 and 5-HT6, 5-HT1 A , 5-HT1 P , 5-HT2, 5-HT3, and 5-HT4 have been reported to be expressed in the gut (16). 5-HT1, 5-HT2, and 5-HT4 receptors are coupled via guanine nucleotide binding (G) proteins to their effectors, whereas 5-HT3 receptor is a ligand-gated ion channel permeable to anions and cations (17).

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The enteric neural receptor for 5-hydroxytryptamine

Cited by 46 publications

References 33 publications

Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro.

Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro.

Peripheral neural serotonin receptors: identification and characterization with specific antagonists and agonists.

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

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