Exogenous motilin affects postprandial proximal gastric motor and sensory function

American Journal of Physiology-Gastrointestinal and Liver Physi

Burggraaf

et al. 2003

This study investigates motilin effects on the proximal stomach in patients with functional dyspepsia (FD) and healthy volunteers. Eight healthy volunteers and 12 patients with FD were infused with synthetic motilin or placebo. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored by visual analog scales. Plasma motilin concentrations were measured by radioimmunoassay. Motilin concentrations and baseline gastric volumes were similar for patients and healthy volunteers. Motilin, compared with placebo, reduced gastric volume by 112 ml [ F(29,195); confidence interval (CI) 95%] in patients and by 96 ml [ F(−7,200); CI 95%] in healthy volunteers. In patients, motilin decreased compliance by 76 ml/mmHg [ F(9,143); CI 95%] compared with placebo, which was similar in volunteers [66 ml/mmHg; F(11,120); CI 95%]. Patients were more nauseous during motilin compared with placebo ( P = 0.04), whereas healthy volunteers did not experience nausea. We conclude that in a fasted condition, FD patients have a similar proximal gastric motor response to motilin as healthy volunteers, but experience an exaggerated sensation of nausea.

Section: Discussionmentioning

confidence: 52%

“…However, motilin reduces postprandial gastric volume in healthy volunteers (6), and impaired relaxation is present in a high proportion of patients (20) In addition, the motilin agonist ABT-229 induced symptom deterioration in FD patients (23).…”

mentioning

confidence: 99%

Motilin effects on the proximal stomach in patients with functional dyspepsia and healthy volunteers

American Journal of Physiology-Gastrointestinal and Liver Physi

Burggraaf

et al. 2003

“…Baseline serum motilin was calculated as the average of the motilin levels from t = 0–40 min. The PK for exogenous motilin were evaluated as reported previously [3, 23]. The RWJ‐68023 PK parameters were the maximal concentration ( C max ) of RWJ‐68023 plasma levels, and the area under the concentration curve from t = 0–135 min (AUC 0−135 ).…”

Section: Methodsmentioning

confidence: 99%

“…Motilin is a gastrointestinal (GI) peptide synthesized and released by enterochromaffin cells in the proximal small intestine [1]. Motilin is involved in the regulation of interdigestive and postprandial GI motility [2, 3]. Disturbed GI motility is a feature observed in functional bowel disorders such as functional dyspepsia (FD) [4–6] and irritable bowel syndrome (IBS) [7, 8].…”

Section: Introductionmentioning

confidence: 99%

“…Disturbed GI motility is a feature observed in functional bowel disorders such as functional dyspepsia (FD) [4–6] and irritable bowel syndrome (IBS) [7, 8]. In healthy volunteers, motilin decreases postprandial gastric volumes similarly to the impaired postprandial relaxation observed in patients with FD [3, 5]. The disturbed GI motility observed in patients’ IBS coincides with altered motilin levels [9–11].…”

Section: Introductionmentioning

confidence: 99%

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Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function

Burggraaf

et al. 2004

Brit J Clinical Pharma

AimTo assess the effects of the motilin receptor antagonist RWJ-68023 on basal and motilin-stimulated proximal gastric volume. MethodsEighteen healthy male volunteers received RWJ-68023 in two different doses or placebo for 135 min. After 45 min, subjects received a motilin infusion for 90 min. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored using visual analogue scales. Motilin and RWJ-68023 concentrations were assessed by radioimmunoassay and liquid chromatography-mass spectrometry, respectively. ResultsBoth dosages of RWJ-68023 were safe and well tolerated. The most common adverse events were of gastrointestinal origin. RWJ-68023 did not affect basal proximal gastric volume, but the high-dose RWJ-68023 reduced the contractile effect of motilin on the stomach. This antagonizing effect of RWJ-68023 was only significant ( P = 0.014) during the distension procedure. ConclusionsThe RWJ-68023 doses used in this study were selected to accomplish plasma concentrations that would block the motilin effect entirely. However, the antagonizing effect of RWJ-68023 was partial and only present when the tonic condition of the stomach was modulated by motilin.

Gallbladder volume as a biomarker for the motilin effect in healthy volunteers and patients with functional dyspepsia

Kam

et al. 2004

Aliment Pharmacol Ther

Self Cite

SUMMARYAim: To investigate a motilin effect on gallbladder volume in healthy volunteers and patients with functional dyspepsia. Methods: Forty-three healthy volunteers and 10 patients with functional dyspepsia received motilin (4 pmol.min/kg) or placebo in four separate doubleblind, randomized, placebo-controlled, cross-over studies. The gallbladder volume was measured by ultrasonography. Analysis of variance of the combined data of these studies was performed to investigate a motilin effect on gallbladder volume and potential differences between patients and healthy volunteers. Results: The baseline gallbladder volume was similar for placebo and motilin treatment, as well as for patients and healthy volunteers. Motilin, compared with placebo, significantly decreased the gallbladder volume in healthy volunteers (P ¼ 0.003) and patients (P < 0.0001). A linear concentration-response relationship was observed. The decrease in gallbladder volume by motilin was greater in patients (P ¼ 0.03). The motilin effect was consistent between studies. Conclusion: The interdigestive gallbladder volume is a non-invasive end-point for motilin activity, displaying a consistent response across studies, a clear response to motilin and a clear concentration-response relationship. However, it is less suitable as a biomarker for future pharmacological studies on motilin agonists or antagonists as the effect is probably indirect, and a relatively large study population of 27 subjects is required to demonstrate a 15% decrease in gallbladder volume. Further investigation is required to confirm altered gallbladder motility as a feature of functional dyspepsia.