Radioisotopic studies of the binding, exchange, and distribution of 5‐hydroxytryptamine synthesized from its radioactivity precursor

Gershon, Michael D.; Ross, Leonard L.

doi:10.1113/jphysiol.1966.sp008046

Cited by 140 publications

(46 citation statements)

References 23 publications

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“…EC cells constitutively secrete 5-HT (Toh, 1954;Schwörer et al, 1987b) and release more when stimulated to do so (Ahlman and Dählstrom, 1983;Grønstad et al, 1985;Schwörer et al, 1987a;Racké et al, 1988;Wingren et al, 1988;Grider et al, 1996). EC cell 5-HT can overflow to the intestinal lumen (Nilsson et al, 1987;Wingren et al, 1988), can be inactivated by uptake and metabolism within the mucosa (Gershon and Ross, 1966a;Pan and Gershon, 2000), or can reach the portal circulation (Toh, 1954;Schwörer et al, 1987b). Free 5-HT in the portal vein is taken up and metabolized in the liver (Blashko and Levine, 1966;Gershon and Ross, 1966a;Gershon, 1977).…”

Section: Discussionmentioning

confidence: 99%

Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters

et al. 2001

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The enteric serotonin reuptake transporter (SERT) has been proposed to play a critical role in serotonergic neurotransmission and in the initiation of peristaltic and secretory reflexes. We analyzed potential compensatory mechanisms and enteric function in the bowels of mice with a targeted deletion of SERT. The guts of these animals were found to lack mRNA encoding SERT; moreover, high-affinity uptake of 5-HT into epithelial cells, mast cells, and enteric neurons was present in the SERT ϩ/ϩ bowel but absent in the SERT Ϫ/Ϫ bowel. However, both the SERT ϩ/ϩ gut and the Ϫ/Ϫ gut expressed molecules capable of transporting 5-HT, but with affinities and selectivity much lower than those of SERT. These included the dopamine transporter (DAT) and polyspecific organic cation transporters OCT-1 and OCT-3. DAT and OCT immunoreactivities were present in both the submucosal and myenteric plexuses, and the OCTs were also located in the mucosal epithelium. 5-HT was found in all of its normal sites in the SERT Ϫ/Ϫ bowel, which contained mRNA encoding tryptophan hydroxylase, but no 5-HT was present in the blood of SERT Ϫ/Ϫ animals. Stool water and colon motility were increased in most SERT Ϫ/Ϫ animals; however, the increase in motility (diarrhea) occasionally alternated irregularly with decreased motility (constipation). The watery diarrhea is probably attributable to the potentiation of serotonergic signaling in SERT Ϫ/Ϫ mice, whereas the transient constipation may be caused by episodes of enhanced 5-HT release leading to 5-HT receptor desensitization.

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Section: Discussionmentioning

confidence: 99%

Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters

et al. 2001

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“…The exocrine pancreatic mechanism for the uptake and metabolism of amino acids L-dopa and L-5HTP has been studied (6)(7)(8)(9)(10)(11)(12)(13). These amino acids are de carboxylated in the exocrine cells, and the corresponding amines can subsequently be me tabolized, probably mainly by oxidative deamination.…”

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confidence: 99%

Amines and the rat exocrine pancreas. 1. Effects of receptor blockers on turnover of L-dopa.

et al. 1979

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Abstract-The acinar cells of the exocrine pancreas have the capacity of efficiently take up and metabolize L-dopa. In the present study, the metabolism of L-dopa by the exocrine pancreas of the rat and effects of receptor blockers on the metabolism were studied by fluorescent histochemical and chemical methods. After i.v. administration of L-dopa (50 mg/kg), a large amount of dopamine (DA) was detected in the exocrine pancreas, and in the pancreatic juice large amounts of DA and its metabolites. DA blockers (haloperidol, sulpiride, and pimozide) and a-blockers (phenoxybenzamine, and phentolamine) produced a significant increase in the accumulation of DA after administration of L-dopa. On the other hand, (I-blockers (propranolol, and oxprenolol) were without effects. The excretion of DA into the pancreatic Juice appeared to be associated with the secretion of zymogen granules, thus DA serves as an indicator of pancreatic secretory activity, especially of enzyme secretion.Because DA and a blockers produced an increase in the accumulation of DA, dopaminergic and/or a adrenergic mechanisms probably exist in the exocrine pancreas of the rat and these mechanisms modify the enzyme secretion.The exocrine pancreas has a great capacity to take up amino acids and analogues of amino acids (1-5) from the blood, presumably reflecting the high protein synthesizing capacity of the organ. The exocrine pancreatic mechanism for the uptake and metabolism of amino acids L-dopa and L-5HTP has been studied (6-13). These amino acids are de carboxylated in the exocrine cells, and the corresponding amines can subsequently be me tabolized, probably mainly by oxidative deamination. These compounds are also taken up and transiently stored in the zymogen granules where they seem to be protected from enzymatic degradation. Reserpine, prenylamine, or desipramine prevented incorporation of DA into the pancreatic zymogen granules (14). These findings suggest that there are similarities, to sonic extent, between the exocrine pancreatic cells and the cells normally synthesizing and storing biogenic monoamines (i.e. adrenergic nerves and certain endocrine cell system).In sonic fluorescent histochernical experiments on the gastro-intestinal organs, we gave ra(s L-dopa and L-5HTP, and noticed that the fluorescence due to L-dopa and L-5HTPinjections was somewhat differently distributed in the exocrine pancreas.There is some possibility that L-dopa and L-5HTP are metabolized in a different manner by the exocrine pancreas, and a large amount of DA and 5-HT, accumulated intracellularly and extracellUlarly, could modify the exocrine pancreatic function. In the present experiments,

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“…From the results in the strip of ileum, 5-HTP itself would he an essentially inactive substance. It is well known that 5-HTP, when administered to various animals, localizes in many tissues and is decarboxylated to 5-HT (12)(13)(14). It is likely, therefore, that the fast contractile response of the intestine to 5-HTP was induced through 5-HT formed locally from the exogenously administered 5-HTP.…”

Section: Discussionmentioning

confidence: 99%

“…Abstract--The mode of actions of' 5-hydroxytryptamine (5-HT) and its derivatives, tryptophan (14)), 5-hydroxytryptophan (5-HTP) and 5-hydroxyindole acetic acid (5-HIAA) vas studied on the isolated, blood-perfused small intestine and isolated ileum strip of rats.…”

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confidence: 99%

Comparative Studies With 5-Hydroxytryptamine and Its Derivatives in Isolated, Blood-Perfused Small Intestine and Tleum Strip of the Rat

Sakai¹,

Akima²,

Shiraki³

1979

Japanese Journal of Pharmacology

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Abstract--The mode of actions of' 5-hydroxytryptamine (5-HT) and its derivatives, tryptophan (14)), 5-hydroxytryptophan (5-HTP) and 5-hydroxyindole acetic acid(5-HIAA) vas studied on the isolated, blood-perfused small intestine and isolated ileum strip of rats.In the isolated, blood-perfused intestinal preparations, 5-HT and 5-HTP injected into the superior mesenteric artery caused a monophasic fast contraction, while TP and 5-HIAA had no effects on the intestine. The contractile responses to 5-HT and 5-HTP were abolished by tetrodotoxin (TTX), hexamethoitium (C5) and morphine, but were resistant to blockade of either atropine, methvsergidc or phentolamine.On the other hand, in the ileum strip preparations, 5-HT contracted the ileum, but its derivatives had no effects on the ileum. TTX, C,;, morphine and atropine failed to prevent the contractile response to 5-HT, whereas methysergide effectively antagonized the response. The present results indicate that 5-HT acts by exciting intramural neuronal elements or by directly contracting the smooth muscle of the intestine.5-HTP seems to act in the same manner as 5-HT.5-Hydroxytryptamine (5-HT) has been shown to contract smooth muscle of the isolated intestine by a direct action on the muscle fibres or by an indirect effect through excita tion of the intrinsic network of nerves (1-5). These findings, however, were obtained in isolated intestinal preparations bathed in physiological salt solutions. In view of this, it was considered that recordings of response of the intestinal smooth muscle with an intact blood supply may reveal features of the intestinal musculature.In the present experiments, we perfused the isolated small intestine of the rat through the superior mesenteric artery with blood from a donor, using a cross-circulation technique. This method enabled injection of drugs into the superior mesenteric artery and We could observe simultaneously vascular and muscular responses of the intestine.Our objective herein was to determine whether comparable information about the actions of 5-HT and its derivatives could he obtained from isolated, blood-perfused small intestine and from isolated ileum strips of the rat. MA I"ERIALS AND M1 THODSMale Sprague-Dawley rats were used.Isolated, 1,/crcnl perJuse~l.enrall intestinc: Donor rats (550-750 g) were anesthetized with pentobarbital sodium (65 mg/kg i.p.). The animal was placed on a table maintained by a

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Radioisotopic studies of the binding, exchange, and distribution of 5‐hydroxytryptamine synthesized from its radioactivity precursor

Cited by 140 publications

References 23 publications

Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters

Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters

Amines and the rat exocrine pancreas. 1. Effects of receptor blockers on turnover of L-dopa.

Comparative Studies With 5-Hydroxytryptamine and Its Derivatives in Isolated, Blood-Perfused Small Intestine and Tleum Strip of the Rat

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