Review Article

The Prokinetic Face of Ghrelin

Table 2

Prokinetic effects of exogenous ghrelin on diseased stomach in vivo. GE: gastric emptying; GHRP-6: ghrelin secretagogue receptor 6 (non-synthetic ghrelin receptor agonist); h: hour; iNOS: inducible nitric oxide synthase; IP: intraperitoneal; IV: intravenous; L-NAME: Nฯ‰-Nitro-L-arginine-methyl-ester-hydrochloride; NO: nitric oxide; Postop: postoperative; SD: Sprague Dawley.

AuthorSpeciesGhrelin typeEffective doseMethodsResultsMechanism of action

Trudel L.,
[29]
Conscious postop ileus model (SD male rats)Human ghrelin-28 (IGBMC, France)20โ€‰ ๐œ‡ g/kg IV given immediately after mealAssessment of GE by gastric retention of a phenol red-marked mealGhrelin reversed the postop delayed GE

Trudel L., [42]Conscious postop ileus model (female mongrel dogs)Ghrelin (IGBMC, France)( i ) 100โ€‰ ๐œ‡ g/kg IV on day 2Assessment of GE by acetaminophen methodGhrelin reversed the postop delayed GE
( i i ) 4โ€‰ ๐œ‡ g/kg IV on day 3
( i i i ) 20โ€‰ ๐œ‡ g/kg IV on day 4given after meal

De Winter B., [33]Conscious LPS septic ileus model (Swiss OFI mice)( i ) Rat ghrelin (Tocris, UK)( i ) Ghrelin: 100โ€‰ ๐œ‡ g/kgAssessment of GE by the gastric retention of an Evans blue-marked mealGhrelin and GHRP-6 accelerated GE in LPS septic ileus mice
( i i ) GHRP-6 (Bachem, UK)( i i ) GHRP-6: 20 and100โ€‰ ๐œ‡ g/kg given IP 1h prior to meal

Poitras P., [31]Conscious postop ileus ยฑ morphine-treated rat model (male SD rats)Ghrelin receptor agonist RC-1139 (Rejuvenon Corp., USA)2.5โ€“10โ€‰mg /Kg IV given immediately after mealAssessment of GE by the retention of 9 9 m Tc-labelled meal( i ) RC-1139 accelerated GE dose-dependently in postop ileus rats
( i i ) RC-1139 at 10โ€‰mg/Kg accelerated GE in postop ileus + morphine-treated rats

Liu Y.,
[43]
Conscious Cisplatin-treated adult male C57/6J black miceRat ghrelin (Bachem Ltd, UK)1โ€‰mg/Kg, IP b.i.dAssessment of gastric emptying by the wet weight of gastric contentGhrelin improved GE

Sallam H.,
[44]
Conscious scald-burned model (SD male rats)Ghrelin (Tocris, USA)2โ€‰nmol/rat given IP 20โ€‰min before mealAssessment of GE by gastric retention of a phenol red-marked mealGhrelin accelerated GE; an effect blocked by pretreatment with atropineGhrelinโ€™s effects on gastric motility involve the cholinergic pathway

Venkova K.,
[45]
Conscious postop ileus ยฑ morphine-treated rat model (male SD rats)Ghrelin receptor agonist TZP-101 (Tranzyme Pharma Canada)0.1โ€“1โ€‰mg /Kg (1ml) IV given 1-2โ€‰min before mealAssessment of GE by the retention of 9 9 m Tc-labelled mealTZP-101 accelerated GE dose-dependently in postop ileus rats ยฑ morphine

Qui et al.
[40]
Diabetic mouse model (IP-alloxan-treated C57 mice)Rat ghrelin
GHRP-6(Tocris, UK)
50โ€“200โ€‰ ๐œ‡ g/Kg given IP prior to mealAssessment of GE by gastric retention of a phenol red-marked mealGhrelin and GHRP-6 at all doses accelerated GE; an effect blocked by atropine or L-NAME.The effects of Ghrelin and GHRP-6 on GE in diabetic gastroparesis is mediated via the cholinergic pathways

Qui et al.
[41]
Diabetic guinea pig model (IP-STZ-treated)Ghrelin
GHRP-6
20, 50 and 100โ€‰ ๐œ‡ g/Kg given IP prior to mealAssessment of GE by gastric retention of a phenol red-marked mealGhrelin and GHRP-6 at all doses accelerated GE; an effect blocked by atropine.The effects of Ghrelin and GHRP-6 on GE in diabetic gastroparesis are mediated via the cholinergic pathways

Chen Y.,
[46]
LPS endotoxemia mouse model (male ICR mice)Rat ghrelin (Global Peptide Services, UDA)20โ€‰ ๐œ‡ g/Kg IP given 15โ€‰min before meal( i ) Assessment of GE by gastric retention of a phenol red-marked meal( i ) Ghrelin had no effect on GEGhrelinโ€™s effect on LPS-delayed GE are mediated via the down regulation of NO
( i i ) Assessment of plasma NO production by fluorometry( i i ) Ghrelin normalized endotoxemia-induced delayed GE
( i i i ) Assessment of iNos expression by immunohistochemistry( i i i ) Ghrelin 20โ€‰ ๐œ‡ g/Kg reduced plasma NO and iNOS expression in the submucosa and musculosa of the stomach

Zheng Q.,
[47]
Diabetic mouse model (IP-alloxan-treated C57 mice)GHRP-6 (Tocris, UK)200โ€‰ ๐œ‡ g/kg given IP prior to mealAssessment of GE by gastric retention of a phenol red-marked mealGHRP-6 accelerated diabetic-induced delayed GE; an effect blocked by pretreatment with atropineGHRP-6 effects on gastric motility involve the cholinergic pathway