Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents
Abstract The gastrointestinal (GI) hormone motilin helps control human stomach movements during hunger and promotes hunger. Although widely present among mammals, it is generally accepted that in rodents the genes for motilin and/or its receptor have undergone pseudonymization, so exogenous motilin...
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.900 |
| _version_ | 1818115451588182016 |
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| author | Gareth J. Sanger |
| author_facet | Gareth J. Sanger |
| author_sort | Gareth J. Sanger |
| collection | DOAJ |
| description | Abstract The gastrointestinal (GI) hormone motilin helps control human stomach movements during hunger and promotes hunger. Although widely present among mammals, it is generally accepted that in rodents the genes for motilin and/or its receptor have undergone pseudonymization, so exogenous motilin cannot function. However, several publications describe functions of low concentrations of motilin, usually within the GI tract and CNS of mice, rats, and guinea pigs. These animals were from institute‐held stocks, simply described with stock names (e.g., “Sprague–Dawley”) or were inbred strains. It is speculated that variation in source/type of animal introduces genetic variations to promote motilin‐sensitive pathways. Perhaps, in some populations, motilin receptors exist, or a different functionally‐active receptor has a good affinity for motilin (indicating evolutionary pressures to retain motilin functions). The ghrelin receptor has the closest sequence homology, yet in non‐rodents the receptors have a poor affinity for each other's cognate ligand. In rodents, ghrelin may substitute for certain GI functions of motilin, but no good evidence suggests rodent ghrelin receptors are highly responsive to motilin. It remains unknown if motilin has functional relationships with additional bioactive molecules formed from the ghrelin and motilin genes, or if a 5‐TM motilin receptor has influence in rodents (e.g., to dimerize with GPCRs and create different pharmacological profiles). Is the absence/presence of responses to motilin in rodents’ characteristic for systems undergoing gene pseudonymization? What are the consequences of rodent supplier‐dependent variations in motilin sensitivity (or other ligands for receptors undergoing pseudonymization) on gross physiological functions? These are important questions for understanding animal variation. |
| first_indexed | 2024-12-11T04:06:50Z |
| format | Article |
| id | doaj.art-dc819d461e544936933a215f97be4bca |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-11T04:06:50Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-dc819d461e544936933a215f97be4bca2022-12-22T01:21:30ZengWileyPharmacology Research & Perspectives2052-17072022-04-01102n/an/a10.1002/prp2.900Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodentsGareth J. Sanger0Blizard Institute and the National Centre for Bowel Research Barts and The London School of Medicine and Dentistry Queen Mary University of London London United KingdomAbstract The gastrointestinal (GI) hormone motilin helps control human stomach movements during hunger and promotes hunger. Although widely present among mammals, it is generally accepted that in rodents the genes for motilin and/or its receptor have undergone pseudonymization, so exogenous motilin cannot function. However, several publications describe functions of low concentrations of motilin, usually within the GI tract and CNS of mice, rats, and guinea pigs. These animals were from institute‐held stocks, simply described with stock names (e.g., “Sprague–Dawley”) or were inbred strains. It is speculated that variation in source/type of animal introduces genetic variations to promote motilin‐sensitive pathways. Perhaps, in some populations, motilin receptors exist, or a different functionally‐active receptor has a good affinity for motilin (indicating evolutionary pressures to retain motilin functions). The ghrelin receptor has the closest sequence homology, yet in non‐rodents the receptors have a poor affinity for each other's cognate ligand. In rodents, ghrelin may substitute for certain GI functions of motilin, but no good evidence suggests rodent ghrelin receptors are highly responsive to motilin. It remains unknown if motilin has functional relationships with additional bioactive molecules formed from the ghrelin and motilin genes, or if a 5‐TM motilin receptor has influence in rodents (e.g., to dimerize with GPCRs and create different pharmacological profiles). Is the absence/presence of responses to motilin in rodents’ characteristic for systems undergoing gene pseudonymization? What are the consequences of rodent supplier‐dependent variations in motilin sensitivity (or other ligands for receptors undergoing pseudonymization) on gross physiological functions? These are important questions for understanding animal variation.https://doi.org/10.1002/prp2.900animal variationexperimental reproducibilitymotilinpseudogenerodent |
| spellingShingle | Gareth J. Sanger Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents Pharmacology Research & Perspectives animal variation experimental reproducibility motilin pseudogene rodent |
| title | Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents |
| title_full | Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents |
| title_fullStr | Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents |
| title_full_unstemmed | Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents |
| title_short | Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents |
| title_sort | why is motilin active in some studies with mice rats and guinea pigs but not in others implications for functional variability among rodents |
| topic | animal variation experimental reproducibility motilin pseudogene rodent |
| url | https://doi.org/10.1002/prp2.900 |
| work_keys_str_mv | AT garethjsanger whyismotilinactiveinsomestudieswithmiceratsandguineapigsbutnotinothersimplicationsforfunctionalvariabilityamongrodents |