The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound

Briejer, M.R.; Bosmans, Jean-Paul; Daele, Paul Van; Jurzak, Mirek; Heylen, Lieve; Leysen, Josée E.; Prins, Nicolaas H.; Schuurkes, J. A. J.

doi:10.1016/s0014-2999(01)01087-1

Cited by 138 publications

(137 citation statements)

References 32 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…Obestatin had no statistically significant ability to reduce the facilitation of EFS-evoked contractions caused by the 5-HT 4 receptor agonist (Briejer et al, 2001) prucalopride, although there was an inhibitory trend for both the 0.1 and 1 mM concentrations. These observations suggest that the ability of obestatin to interact with the functions of ghrelin may be a nonspecific activity, independent of direct proteinprotein interactions and consistent with the inability of obestatin to interact with the ghrelin binding site, also reported by Zhang et al (2005).…”

Section: Discussionmentioning

confidence: 88%

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Bassil

Häglund

Brown

et al. 2007

British J Pharmacology

View full text Add to dashboard Cite

Background and purpose: Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated. Experimental approach: Rat GI motility was studied in vitro (jejunum contractility and cholinergically-mediated contractions of forestomach evoked by electrical field stimulation; EFS) and in vivo (gastric emptying and intestinal myoelectrical activity). Ghrelin receptor function was studied using a GTPgS assay and transfected cells. Key results: Contractions of the jejunum or forestomach were unaffected by obestatin 100 nM or 0.01-1000 nM, respectively (P40.05 each; n ¼ 4-18). Obestatin (0.1-1 nM) reduced the ability of ghrelin 1 mM to facilitate EFS-evoked contractions of the stomach (increases were 42.777.8% and 21.275.0 % in the absence and presence of obestatin 1 nM; Po0.05; n ¼ 12); higher concentrations (10-1000 nM) tended to reduce the response to ghrelin but changes were not statistically significant. Similar concentrations of obestatin did not significantly reduce a facilitation of contractions caused by the 5-HT 4 receptor agonist prucalopride, although an inhibitory trend occurred at the higher concentrations (increases were 69.3714.0% and 42.678.7% in the absence and presence of 1000 nM obestatin; n ¼ 10). Obestatin (up to 10 mM) did not modulate recombinant ghrelin receptor function. Ghrelin increased gastric emptying and reduced MMC cycle time; obestatin (1000 and 30,000 pmol kg À1 min À1 ) had no effects. Obestatin (2500 pmol kg À1 min À1 , starting 10 min before ghrelin) did not prevent the ability of ghrelin (500 pmol kg À1 min À1 ) to shorten MMC cycle time. Conclusions and implications: Obestatin has little ability to modulate rat GI motility.

show abstract

Section: Discussionmentioning

confidence: 88%

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Bassil

Häglund

Brown

et al. 2007

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…The e ect of the selective 5-HT 4 receptor agonist prucalopride in both preparations pointed clearly to interactions with 5-HT 4 receptors. Prucalopride expresses nanomolar a nity for 5-HT 4 receptors and possesses approximately 1000 fold selectivity for 5-HT 4 receptors over other 5-HT receptors (Briejer et al, 1998c; Janssen Research Foundation; data on ®le). Thus, the concentration used in this study (0.3 mM) producing an e ect, strongly suggested 5-HT 4 receptor involvement.…”

Section: Discussionmentioning

confidence: 99%

5‐HT₄ receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

Prins

Akkermans

Lefebvre

et al. 2000

British J Pharmacology

View full text Add to dashboard Cite

1 5-HT 4 receptors mediate circular muscle relaxation in both human and canine large intestine, but this phenomenon alone can not explain the improvement in colonic motility induced by selective 5-HT 4 receptor agonists in vivo. We set out to characterize 5-HT 4 receptor-mediated e ects in longitudinal muscle strips of canine and human large intestine. 2 Electrical ®eld stimulation (EFS) was applied providing submaximal isotonic contractions. L-NOARG (0.1 mM) was continuously present in the organ bath to preclude nitric oxide-induced relaxation to EFS. 3 The selective 5-HT 4 receptor agonist prucalopride (0.3 mM) enhanced EFS-evoked contractions, that were antagonized in both preparations by the selective 5-HT 4 receptor antagonist GR 113808 (0.1 mM). The prucalopride-induced increase was present in canine ascending and descending colon, but absent in rectum. Regional di erences in response to prucalopride were not observed in human ascending and sigmoid colon and rectum. Incubation with atropine (1 mM) or tetrodotoxin (0.3 mM) inhibited EFS-induced contractions, which were then una ected by prucalopride (0.3 mM) in both tissues. 4 In the presence of methysergide (3 mM; both tissues) and granisetron (0.3 mM; only human tissues), 5-HT (0.3 mM) enhanced EFS-induced contractions, an e ect that was antagonized by GR 113808 (0.1 mM). In the presence of atropine or tetrodotoxin, EFS-induced contractions were inhibited, leaving 5-HT (0.3 mM) ine ective in both preparations. 5 This study demonstrates for the ®rst time that in human and canine large intestine, 5-HT 4 receptors are located on cholinergic neurones, presumably mediating facilitating release of acetylcholine, resulting in enhanced longitudinal muscle contractility. This study and previous circular muscle strip studies suggest that 5-HT 4 receptor agonism facilitates colonic propulsion via a coordinated combination of inhibition of circumferential resistance and enhancement of longitudinal muscle contractility.

show abstract

“…Прукалоприд является высокоселективным агонистом и обладает высоким срод-ством к рецепторам 5-НТ 4 , способствующим холинергиче-ской нейротрансмиссии в кишечных нейронах. Прукало-прид демонстрирует высокое аффинное связывание с изоформами рецептора 5-HT 4а и 5-HT 4b человека при значениях активности связывания (pK i ) 8,6 и 8,1 соответ-ственно [31]. Прукалоприд также проявляет очень высокую специфичность для изоформ рецепторов 5-HT 4 с более чем 290-кратной селективностью, показывающих измери-мое сродство к прукалоприду (к рецептору дофамина D 4 человека с pK i 5,63, к рецептору 5-HT 3 мыши с pK i 5,41, к человеческому σ1-рецептору с pK i 5,43) [31].…”

Section: фармакология и механизм действияunclassified

“…Прукало-прид демонстрирует высокое аффинное связывание с изоформами рецептора 5-HT 4а и 5-HT 4b человека при значениях активности связывания (pK i ) 8,6 и 8,1 соответ-ственно [31]. Прукалоприд также проявляет очень высокую специфичность для изоформ рецепторов 5-HT 4 с более чем 290-кратной селективностью, показывающих измери-мое сродство к прукалоприду (к рецептору дофамина D 4 человека с pK i 5,63, к рецептору 5-HT 3 мыши с pK i 5,41, к человеческому σ1-рецептору с pK i 5,43) [31]. Связывание прукалоприда с G-белком 5-HT 4 -рецептором активирует аденилатциклазу и увеличивает уровень внутриклеточного циклического аденозинмонофосфата (AMP) [32].…”

Section: фармакология и механизм действияunclassified

Prukalopride in the Treatment of Chronic Constipation

Плотникова¹,

Грачева²

2017

Med. sov.

View full text Add to dashboard Cite

The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound

Cited by 138 publications

References 32 publications

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

5‐HT₄ receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

Prukalopride in the Treatment of Chronic Constipation

Contact Info

Product

Resources

About

The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound

Cited by 138 publications

References 32 publications

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

5‐HT4 receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

Prukalopride in the Treatment of Chronic Constipation

Contact Info

Product

Resources

About

5‐HT₄ receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle