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Impaired relaxation...
Impaired relaxation of stomach smooth muscle in mice lacking cyclic GMP-dependent protein kinase I
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- Ny, L (författare)
- Lund University Hospital
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- Pfeifer, A (författare)
- Salk Institute
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- Aszodi, A (författare)
- Lund University Hospital
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- Ahmad, M (författare)
- Lund University Hospital
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- Alm, P (författare)
- Lund University Hospital
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- Hedlund, Petter (författare)
- Lund University Hospital
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- Fassler, R (författare)
- Lund University Hospital
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- Andersson, KE (författare)
- Lund University Hospital
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(creator_code:org_t)
- 2009-01-30
- 2000
- Engelska.
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Ingår i: British Journal of Pharmacology. - : Wiley-Blackwell. - 0007-1188 .- 1476-5381. ; 129:2, s. 395-401
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 1. Guanosine 3', 5'-cyclic monophosphate (cyclic GMP)-dependent kinase I (cGKI) is a major receptor for cyclic GMP in a variety of cells. Mice lacking cGKI exhibit multiple phenotypes, including severe defects in smooth muscle function. We have investigated the NO/cGMP- and vasoactive intestinal polypeptide (VIP)/adenosine 3', 5'-cyclic monophosphate (cyclic AMP)-signalling pathways in the gastric fundus of wild type and cGKI-deficient mice. 2. Using immunohistochemistry, similar staining patterns for NO-synthase, cyclic GMP- and VIP-immunoreactivities were found in wild type and cGKI-deficient mice. 3. In isolated, endothelin-1 (3 nM - 3 microM)-contracted, muscle strips from wild type mice, electrical field stimulation (1 - 16 Hz) caused a biphasic relaxation, one initial rapid, followed by a more slowly developing phase. In preparations from cGKI-deficient mice only the slowly developing relaxation was observed. 4. The responses to the NO donor, SIN-1 (10 nM - 100 microM), and to 8-Br-cyclic GMP (10 nM - 100 microM) were markedly impaired in strips from cGKI-deficient mice, whereas the responses to VIP (0.1 nM - 1 microM) and forskolin (0.1 nM - 1 microM) were similar to those in wild type mice. 5. These results suggest that cGKI plays a central role in the NO/cGMP signalling cascade producing relaxation of mouse gastric fundus smooth muscle. Relaxant agents acting via the cyclic AMP-pathway can exert their effects independently of cGKI.
Nyckelord
- cyclic GMP
- enteric nervous system
- nitric oxide
- non-adrenergic non-cholinergic (NANC)
- vasoactive intestinal polypeptide
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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