Receptors involved n the action of 5-HT and tryptamine on the isolated rat stomach fundus preparation

Frankhuijzen, A.L.; Bonta, I. L.

doi:10.1016/0014-2999(74)90231-3

Cited by 48 publications

(6 citation statements)

References 22 publications

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“…1986;Baird & Cuthbert 1987;Sjoqvist et al 1992). Furthermore, methysergide has been reported with a varying efficacy to block 5-HT-induced GI contractions (Frankhuijzen & Bonta 1974;Buchheit et ul. 1985;Boeckxstaens et al, 1990), and to influence blood flow in the periphery (Apperley et ul.…”

Section: Intestinal 5-ht Receptor Subtypes and Intestinal Secretionmentioning

confidence: 99%

SEROTONIN ‐ AN INTESTINAL SECRETAGOGUE ‐ Receptor Subtypes and Intracellular Mediators

Hansen¹

1995

Pharmacology & Toxicology

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Section: Intestinal 5-ht Receptor Subtypes and Intestinal Secretionmentioning

confidence: 99%

SEROTONIN ‐ AN INTESTINAL SECRETAGOGUE ‐ Receptor Subtypes and Intracellular Mediators

Hansen¹

1995

Pharmacology & Toxicology

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“…However, other evidence has suggested the existence of two receptors one for tryptamine and one for 5-HT. Thus different receptors for tryptamine and 5-HT have been shown in the rat stomach fundus preparation (Frankhuijzen & Bonta, 1974), and other workers have concluded the existence of different receptors from in vivo studies involving differential antagonism of various pharmacological responses (Clineschmidt & Lotti, 1974;Quock & Weick, 1978). However, these studies have relied on indirect methods for increasing central 5-HT concentrations and therefore are difficult to interpret.…”

Section: Introductionmentioning

confidence: 99%

Different Hypothalamic Receptors Mediate 5‐hydroxytryptamine‐ and Tryptamine‐induced Core Temperature Changes in the Rat

Cox¹,

Lee²,

Martin³

1981

British J Pharmacology

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1Unilateral intrahypothalamic injection of 5-hydroxytryptamine (5-HT) caused a dose-related fall in core temperature in rats, whereas injection of tryptamine into the same site caused a dose-related rise in core temperature. 2 The core temperature changes induced by 5-HT or tryptamine were inhibited by intrahypothalamic pretreatment with indoleamine receptor antagonists in a dose-related manner.3 Other neurotransmitter antagonists, haloperidol, atropine, phentolamine and (-Y)propranolol, had no significant effect on core temperature changes induced by 5-HT or tryptamine. 4 A differential antagonism was observed for the indoleamine receptor antagonists against 5-HT and tryptamine-induced core temperature changes. Methergoline and triflupromazine were more selective against tryptamine-induced hyperthermia, while cyproheptadine was more selective against 5-HT-induced hypothermia. 5 Intrahypothalamic pretreatment with 5,7-dihydroxytryptamine (5,7-DHT) 42 nmol in 2 Al inhibited tryptamine-induced hyperthermia, but was without effect on 5-HT-induced hypothermia. 6 These results suggest the possible existence of two different receptor populations within the preoptic anterior hypothalamus in rats; one specific for 5-HT and the other for tryptamine.

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“…In previous studies of antagonism of serotonin in rat stomach fundus, the reduction of maximum response in the presence of high concentrations of antagonist has been attributed to antagonist-induced conformational alteration of the receptor. 21) Our results suggest that alkaline pH facilitates such alterations, which can be responsible for the small differences on the shifts of 5-HT CRC caused by compound 2 at pH 8 and 7.4.…”

Section: Influence Of Ph On Thementioning

confidence: 61%

Influence of pH on the Binding of Diphenylmethylenepiperidines by 5-HT2B Receptors in Rat Stomach Fundus.

Honrubia

Rodrigo

Cadavid

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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The 5-hydroxytryptamine 2 (5-HT 2 ) receptor class comprises three subtypes 5-HT 2A , 5-HT 2B , 5-HT 2C , which are similar in terms of their sequence, molecular structure, pharmacology and signal transduction pathways.1) All of them belong to the G-protein-coupled-receptors superfamily. They are preferentially coupled to Gq/11 to increase the hydrolysis of inositol phosphates and elevate cytosolic calcium.2)The 5-HT 2B receptor, first found in rat stomach fundus, 3) was one of the latest to be characterised and cloned in mouse, rat and human. [4][5][6][7] As the rest of the 5-HT 2 receptors, 5-HT 2B mediates the release of phosphoinositides, although controversy persists on the possible involvement of other second messengers. [6][7][8][9][10][11][12][13] Interest in the 5-HT 2B receptor has mushroomed as the result of its presence in humans, in both the central nervous system and peripheral tissues. 6,7,14,15) Cyproheptadine (Fig. 1) was chosen as the lead compound for this research project because of its high affinity at 5-HT 2B receptors in rat stomach fundus. In a previous work, 16) we demonstrated the relevance of the amino group in open cyproheptadine analogues. Only compounds having N-H or N-methyl motifs (compounds 1 and 2: 4-diphenylmethylenepiperidine and 4-diphenylmethylene-1-methylpiperidine, respectively), showed significant 5-HT 2B antagonistic activity. This observation supports the previously postulated key role of a cationic amino group in the interaction of ligands at the active site of the aminergic G-coupled protein receptors, by interacting with a conserved anionic aspartate located in the third transmembrane a-helix (TMH) of the receptor. 17)However, a surprising result of our previous study was the total lack of activity of the corresponding quaternary ammonium ion (compound 3: 4-diphenylmethylene-1,1-dimethylpiperidinium iodide). 16)The pH of the biological medium is responsible for the changes in the potency of antagonists at some receptors.18) A question therefore arises whether ligand protonation favours their interaction with 5-HT 2B receptors. To provide new insights on this issue, in this work we studied the influence of increasing the protonation of compounds 2 and 3 (by reducing the pH of the medium) on the antagonism of serotonin in rat stomach fundus preparations. Results and DiscussionDuring the experiments described below, we verified that the pH of the solutions (6, 7.4, 8) remained unchanged over the duration of organ bath experiments (Fig. 2). Cyproheptadine is one of the compounds exhibiting the highest activity at 5-HT 2B receptors. In a previous work we analysed the relevance of the amino group in diphenylmethylenepiperidines (DPMP), which are open cyproheptadine analogues. Only compounds containing N-H or N-methyl motifs, showed significant 5-HT 2B activity. Surprisingly, the corresponding quaternary ammonium salt demonstrated a total lack of activity. Therefore, the question arises whether protonation favours the interaction of these compounds with 5-HT 2B receptors. C...

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Receptors involved n the action of 5-HT and tryptamine on the isolated rat stomach fundus preparation

Cited by 48 publications

References 22 publications

SEROTONIN ‐ AN INTESTINAL SECRETAGOGUE ‐ Receptor Subtypes and Intracellular Mediators

SEROTONIN ‐ AN INTESTINAL SECRETAGOGUE ‐ Receptor Subtypes and Intracellular Mediators

Different Hypothalamic Receptors Mediate 5‐hydroxytryptamine‐ and Tryptamine‐induced Core Temperature Changes in the Rat

Influence of pH on the Binding of Diphenylmethylenepiperidines by 5-HT2B Receptors in Rat Stomach Fundus.

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