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.
| Author | Species | Ghrelin type | Effective dose | Methods | Results | Mechanism of action |
|---|---|---|---|---|---|---|
| De Winter B., [33] |
Conscious healthy and LPS septic ileus model (Swiss OFI mice) | (i) Rat ghrelin (Tocris, UK) | (i) Ghrelin: 100 μg/kg | Assessment of IT by the transit of an Evans blue-marked meal | Ghrelin and GHRP-6, at either dose] had no prokinetic effect on IT in healthy or diseased mice. | |
| (ii) GHRP-6 (Bachem, UK) | (ii) GHRP-6: 20 and100 μg/kg IP 1h prior to meal | |||||
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| Sallam H., [44] | Conscious scald-burned model (SD male rats) | Ghrelin (Tocris, USA) | 2 nmol/rat given IP 20 min before meal | (ii) Assessment of IT and CT by the transit of a phenol red-marked meal | Ghrelin accelerated IT but had no effect on CT | Ghrelin's effects on intestinal motility are mediated via the cholinergic pathway |
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| 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 meal | Assessment of IT by the transit of 99mTc-labelled meal | TZP-101 accelerated IT dose-dependently in postop ileus rats ± morphine | |
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| Zheng Q., [47] |
Conscious diabetic mouse model (IP-alloxan-treated C57 mice) | GHRP-6 (Tocris, UK) | 200 μg/kg given IP prior to meal | Assessment of IT and CT by the transit of a phenol red-marked meal | GHRP-6 accelerated IT, but not CT; an effect blocked by pretreatment with atropine | GHRP-6 effects on intestinal motility involve the cholinergic pathway |
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| 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 μg/Kg given PO 5 min prior to meal | Assessment of IT by percentage of distance of charcoal travelled/total length of small intestine | EX-1314 reversed opiate-induced delayed IT | |
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|
Chen Y., [46] |
LPS endotoxemia mouse model (male ICR mice) | Rat ghrelin (Global Peptide Services, UDA) | 20 μg/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 IT | Ghrelin's effect on LPS-delayed IT transit is mediated via the down regulation of NO |
| (ii) Assessment of plasma NO production by fluorometry | (ii) Ghrelin reduced plasma NO and iNOS expression in the submucosa and musculosa of the duodenum | |||||
| (iii) Assessment of iNos expression by immunohisto-chemistry | ||||||
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| 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 surgery | Assessment of CT by monitoring the time of appearance and weight of fecal pellet output marked with trypan blue dye | TZP-101 accelerated CT dose-dependently at 12 and 24 h after surgery | |
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|
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 dye | Ipamorelin and GHRP-6 accelerated CT 48 h after surgery | |
| (ii) GHRP-6 (Sigma-Aldrich, MO) | (ii) GHRP-6 20 μg/Kg IV bolus given after dosing of 4 doses/ day at 3 h intervals for 2 days after surgery | |||||