| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GASTRIC MOTILITY |
Centre for Gastroenterological Research, Catholic University of Leuven, Leuven, Belgium
Correspondence to:
Correspondence to:
Professor I Depoortere
Centre for Gastroenterological Research, Gasthuisberg O&N, box 701, B-3000 Leuven, Belgium; inge.depoortere{at}med.kuleuven.be
ABSTRACT
Background and aims: The gastroprokinetic activities of ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R), prompted us to compare the effect of ghrelin with that of synthetic peptide (growth hormone releasing peptide 6 (GHRP-6)) and non-peptide (capromorelin) GHS-R agonists both in vivo and in vitro.
Methods: In vivo, the dose dependent effects (1–150 nmol/kg) of ghrelin, GHRP-6, and capromorelin on gastric emptying were measured by the 14C octanoic breath test which was adapted for use in mice. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), or D-Lys3-GHRP-6 (GHS-R antagonist) on the gastroprokinetic effect of capromorelin was also investigated. In vitro, the effect of the GHS-R agonists (1 µM) on electrical field stimulation (EFS) induced responses was studied in fundic strips in the absence and presence of L-NAME.
Results: Ghrelin, GHRP-6, and capromorelin accelerated gastric emptying in an equipotent manner, with bell-shaped dose-response relationships. In the presence of atropine or L-NAME, which delayed gastric emptying, capromorelin failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying but did not effectively block the action of the GHS-R agonists, but this may be related to interactions with other receptors. EFS of fundic strips caused frequency dependent relaxations that were not modified by the GHS-R agonists. L-NAME turned EFS induced relaxations into cholinergic contractions that were enhanced by ghrelin, GHRP-6, and capromorelin.
Conclusion: The 14C octanoic breath test is a valuable technique to evaluate drug induced effects on gastric emptying in mice. Peptide and non-peptide GHS-R agonists accelerate gastric emptying of solids in an equipotent manner through activation of GHS receptors, possibly located on local cholinergic enteric nerves.
Abbreviations: GH, growth hormone; GHS, growth hormone secretagogue; GHS-R, growth hormone secretagogue receptor; GHRP-6, growth hormone releasing peptide 6; L-NAME, NG-nitro-L-arginine methyl ester hydrochloride; EFS, electrical field stimulation
Keywords: ghrelin; gastric emptying; breath test; organ bath; electrical field stimulation
Relevant Article
Gut 2005 54: 1051.
This article has been cited by other articles:
|
|
 |
|
  G. L. Fraser, H. R. Hoveyda, and G. S. Tannenbaum Pharmacological Demarcation of the Growth Hormone, Gut Motility and Feeding Effects of Ghrelin Using a Novel Ghrelin Receptor Agonist Endocrinology, December 1, 2008; 149(12): 6280 - 6288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Taniguchi, H. Ariga, J. Zheng, K. Ludwig, C. Mantyh, T. N. Pappas, and T. Takahashi Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats Am J Physiol Gastrointest Liver Physiol, August 1, 2008; 295(2): G403 - G411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ariga, K. Imai, C. Chen, C. Mantyh, T. N. Pappas, and T. Takahashi Does ghrelin explain accelerated gastric emptying in the early stages of diabetes mellitus? Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1807 - R1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Choi, J. Zhu, G. J. Stoltz, S. Vernino, M. Camilleri, J. H. Szurszewski, S. J. Gibbons, and G. Farrugia Determination of gastric emptying in nonobese diabetic mice Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G1039 - G1045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wierup, M. Bjorkqvist, B. Westrom, S. Pierzynowski, F. Sundler, and K. Sjolund Ghrelin and Motilin Are Cosecreted from a Prominent Endocrine Cell Population in the Small Intestine J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3573 - 3581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Sallam, H. M. Oliveira, H. T. Gan, D. N. Herndon, and J. D. Z. Chen Ghrelin improves burn-induced delayed gastrointestinal transit in rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R253 - R257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimizu, E. C. Chang, A. D. Shafton, D. M. Ferens, G. J. Sanger, J. Witherington, and J. B. Furness Evidence that stimulation of ghrelin receptors in the spinal cord initiates propulsive activity in the colon of the rat J. Physiol., October 1, 2006; 576(1): 329 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Levin, T. Edholm, P. T. Schmidt, P. Gryback, H. Jacobsson, M. Degerblad, C. Hoybye, J. J. Holst, J. F. Rehfeld, P. M. Hellstrom, et al. Ghrelin Stimulates Gastric Emptying and Hunger in Normal-Weight Humans J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3296 - 3302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Tack, I Depoortere, R Bisschops, C Delporte, B Coulie, A Meulemans, J Janssens, and T Peeters Influence of ghrelin on interdigestive gastrointestinal motility in humans Gut, March 1, 2006; 55(3): 327 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. De Smet, I. Depoortere, D. Moechars, Q. Swennen, B. Moreaux, K. Cryns, J. Tack, J. Buyse, B. Coulie, and T. L. Peeters Energy Homeostasis and Gastric Emptying in Ghrelin Knockout Mice J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 431 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T L Peeters Ghrelin: a new player in the control of gastrointestinal functions Gut, November 1, 2005; 54(11): 1638 - 1649. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
