Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats.
OBJECTIVE
Although it has been shown that des-acyl ghrelin decreases food intake and gastric emptying, no previous studies have examined the effects of des-acyl ghrelin on physiologic fed and fasted motor activity in the gastrointestinal tract.


METHODS
We examined the effects of intraperitoneal (IP) administration of des-acyl ghrelin on food intake and the effects of intracerebroventricular (ICV) or intravenous (IV) administration of des-acyl ghrelin on gastroduodenal motility using freely moving conscious rat models. The brain nuclei responding to these effects were examined by c- fos immunohistochemistry of the brain sections.


RESULTS
IP injection of des-acyl ghrelin decreased food intake, and this effect was not altered by capsaicin treatment. IP injection of des-acyl ghrelin enhanced c- fos expression in the arcuate and paraventricular nucleus but not in the nucleus of the solitary tract. Both ICV and IV injection of des-acyl ghrelin disrupted fasted motor activity in the antrum but not in the duodenum. Changes in gastric motility induced by IV injection of des-acyl ghrelin were completely antagonized by ICV injection of a selective corticotropin-releasing factor (CRF) 2 receptor antagonist; however, the CRF 1 receptor antagonist had no effects.


CONCLUSIONS
The results suggest that des-acyl ghrelin decreases food intake and disrupts the fasted motor activity of the antrum in freely moving conscious rats. Peripheral des-acyl ghrelin may induce this function by direct activation of brain receptor by crossing the blood-brain barrier but not by the activation of vagal afferent pathways. In the brain, CRF 2 receptor, but not CRF 1 receptor, is involved in this action.
Chen
Chih-Yen
CY
Division of Gastroenterology, Taipei Veterans General Hospital, Taiwan.
Inui
Akio
A
Asakawa
Akihiro
A
Fujino
Kazunori
K
Kato
Ikuo
I
Chen
Chih-Chuan
CC
Ueno
Naohiko
N
Fujimiya
Mineko
M
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003243:Consciousness; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D005215:Fasting; D005746:Gastric Emptying / Q000187:drug effects*; D054439:Ghrelin; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015167:Vagotomy, Truncal; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D000099052:CRF Receptor, Type 1
C471210:2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; D000814:Aniline Compounds; C101531:CRF receptor type 2; D054439:Ghrelin; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D036361:Peptide Hormones; D016760:Proto-Oncogene Proteins c-fos; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; C116607:antisauvagine 30; C422650:ghrelin, des-n-octanoyl; C104416:astressin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D002211:Capsaicin