Impaired relaxation of stomach smooth muscle in mice lacking cyclic GMP-dependent protein kinase I
2000 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 129, no 2, 395-401 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Wiley-Blackwell , 2000. Vol. 129, no 2, 395-401 p.
cyclic GMP, enteric nervous system, nitric oxide, non-adrenergic non-cholinergic (NANC), vasoactive intestinal polypeptide
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-59771DOI: 10.1038/sj.bjp.0703061.ISI: 85046000024PubMedID: 10694248OAI: oai:DiVA.org:liu-59771DiVA: diva2:353380