Review Article

The Prokinetic Face of Ghrelin

Table 4

Prokinetic effects of exogenous ghrelin on intestinal motility in vivo in disease. CT: colon transit; GHRP-6: ghrelin secretagogue receptor 6 (non-synthetic ghrelin receptor agonist); h: hour; ICV: intracerebrovascular; iNOS: inducible nitric oxide synthase; IP: intraperitoneal; IT: intestinal transit; IV: intravenous; LPS: lipopolysaccharide; NO: nitric oxide; NPY: neuropeptide Y; Postop: postoperative; SC: subcutaneous; SD: Sprague Dawley.

AuthorSpeciesGhrelin typeEffective doseMethodsResultsMechanism of action

De Winter B.,
[33]
Conscious healthy and LPS septic ileus model (Swiss OFI mice)( i ) Rat ghrelin (Tocris, UK)( i ) Ghrelin: 100  𝜇 g/kgAssessment of IT by the transit of an Evans blue-marked mealGhrelin and GHRP-6, at either dose] had no prokinetic effect on IT in healthy or diseased mice.
( i i ) GHRP-6 (Bachem, UK)( i i ) GHRP-6: 20 and100  𝜇 g/kg IP 1h prior to meal

Sallam H., [44]Conscious scald-burned model (SD male rats)Ghrelin (Tocris, USA)2 nmol/rat given IP 20 min before meal( i i ) Assessment of IT and CT by the transit of a phenol red-marked mealGhrelin accelerated IT but had no effect on CTGhrelin’s effects on intestinal motility are mediated via the cholinergic pathway

Venkova K.,
[45]
Conscious postop ileus ± morphine-treated rat model (male SD rats)Ghrelin receptor agonist TZP-101 (Tranzyme Pharma Canada)0.3–1 mg /Kg (1ml) IV given 1-2 min before mealAssessment of IT by the transit of 9 9 m Tc-labelled mealTZP-101 accelerated IT dose-dependently in postop ileus rats ± morphine

Zheng Q.,
[47]
Conscious diabetic mouse model (IP-alloxan-treated C57 mice)GHRP-6 (Tocris, UK)200  𝜇 g/kg given IP prior to mealAssessment of IT and CT by the transit of a phenol red-marked mealGHRP-6 accelerated IT, but not CT; an effect blocked by pretreatment with atropineGHRP-6 effects on intestinal motility involve the cholinergic pathway

Charoenthong-trakul S.,
[32]
Conscious opiate-induced bowel disorder mice model (male lean C57BL/6 mice)Ghrelin receptor agonist EX-1314 (Elixir Pharma-ceuticals)300  𝜇 g/Kg given PO 5 min prior to mealAssessment of IT by percentage of distance of charcoal travelled/total length of small intestineEX-1314 reversed opiate-induced delayed IT

Chen Y.,
[46]
LPS endotoxemia mouse model (male ICR mice)Rat ghrelin (Global Peptide Services, UDA)20  𝜇 g/Kg IP given 15 min before meal( i ) Assessment of IT by the of distance charcoal travelled/total length of small intestine( i ) Ghrelin normalized endotoxemia-induced delayed ITGhrelin’s effect on LPS-delayed IT transit is mediated via the down regulation of NO
( i i ) Assessment of plasma NO production by fluorometry( i i ) Ghrelin reduced plasma NO and iNOS expression in the submucosa and musculosa of the duodenum
( i i i ) Assessment of iNos expression by immunohisto-chemistry

Fraser G.,
[68]
Conscious postop ileus rat model (male SD rats)( i ) Ghrelin receptor agonist TZP-101 (Tranzyme Pharma, Canada)0.3–1 mg /Kg (t.i.d) IV given at 15 min, 2 and 4 h after surgeryAssessment of CT by monitoring the time of appearance and weight of fecal pellet output marked with trypan blue dyeTZP-101 accelerated CT dose-dependently at 12 and 24 h after surgery

Venkova K.,
[69]
Conscious postop ileus rat model (male SD rats)( i ) Ghrelin receptor agonist and selective growth hormone secretagogue ipamorelin (Albany Molecular Research, Inc., NY)( i ) Ipamorelin
1 mg /Kg IV one dose or 0.1 repetitive doses
Assessment of CT by monitoring the time of appearance and weight of fecal pellet output marked with trypan blue dyeIpamorelin and GHRP-6 accelerated CT 48 h after surgery
( i i ) GHRP-6 (Sigma-Aldrich, MO)( i i ) GHRP-6 20  𝜇 g/Kg IV bolus given after dosing of 4 doses/ day at 3 h intervals for 2 days after surgery