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Receptor-mediated i...
Receptor-mediated inhibition of small bowel migrating complex by GLP-1 analog ROSE-010 delivered via pulmonary and systemic routes in the conscious rat
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- Hellström, Per M. (författare)
- Uppsala universitet,Gastroenterologi/hepatologi
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Smithson, A. (författare)
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Stowell, G. (författare)
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Greene, S. (författare)
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Kenny, E. (författare)
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Damico, C. (författare)
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Leone-Bay, A. (författare)
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Baughman, R. (författare)
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Grant, M. (författare)
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Richardson, P. (författare)
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(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- Engelska.
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 179:1-3, s. 71-76
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Background: ROSE-010, a Glucagon-Like Peptide-1 (GLP-1) analog, reduces gastrointestinal motility and relieves acute pain in patients with irritable bowel syndrome (IBS). The rat small bowel migrating myoelectric complex (MMC) is a reliable model of pharmacological effects on gastrointestinal motility. Accordingly, we investigated whether ROSE-010 works through GLP-1 receptors in gut musculature and its effectiveness when administered by pulmonary inhalation. Materials and methods: Rats were implanted with bipolar electrodes at 5, 15 and 25 cm distal to pylorus and myoelectric activity was recorded. First, intravenous or subcutaneous injections of ROSE-010 or GLP-1 (1, 10, 100 mu g/kg) with or without the GLP-1 receptor blocker exendin(9-39)amide (300 mu g/kg.h), were studied. Second, ROSE-010 (100, 200 mu g/kg) Technosphere (R) powder was studied by inhalation. Results: The baseline MMC cycle length was 17.5 +/- 0.8 min. GLP-1 and ROSE-010. administered intravenously or subcutaneously, significantly inhibited myoelectric activity and prolonged MMC cycling; 100 mu g/kg completely inhibited spiking activity for 49.1 +/- 4.2 and 73.3 +/- 7.7 min, while the MMC cycle length increased to 131.1 +/- 11.4 and 149.3 +/- 15.5 min, respectively. Effects of both drugs were inhibited by exendin(9-39) amide. Insufflation of ROSE-010 (100, 200 mu g/kg) powder formulation totally inhibited myoelectric spiking for 52.6 +/- 5.8 and 70.1 +/- 5.4 min, and increased MMC cycle length to 102.6 +/- 18.3 and 105.9 +/- 9.5 min, respectively. Conclusions: Pulmonary delivery of ROSE-010 inhibits gut motility through the GLP-1R similar to natural GLP-1. ROSE-010 causes receptor-mediated inhibition of MMC comparable to that of intravenous or subcutaneous administration. This suggests that ROSE-010 administered as a Technosphere (R) inhalation powder has potential in IBS pain management and treatment.
Nyckelord
- Gastrointestinal motility
- IBS
- Irritable bowel syndrome
- Glucagon
- Pulmonary delivery
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- art (ämneskategori)
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- Av författaren/redakt...
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Hellström, Per M ...
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Smithson, A.
-
Stowell, G.
-
Greene, S.
-
Kenny, E.
-
Damico, C.
-
visa fler...
-
Leone-Bay, A.
-
Baughman, R.
-
Grant, M.
-
Richardson, P.
-
visa färre...
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Regulatory Pepti ...
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Uppsala universitet