Alterations of GTP-binding proteins (GS alpha and Gq/11 alpha) in gastric smooth muscle cells from streptozotocin-induced and WBN/Kob diabetic rats

Citation
S. Lin et al., Alterations of GTP-binding proteins (GS alpha and Gq/11 alpha) in gastric smooth muscle cells from streptozotocin-induced and WBN/Kob diabetic rats, DIG DIS SCI, 45(8), 2000, pp. 1517-1524
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
DIGESTIVE DISEASES AND SCIENCES
ISSN journal
0163-2116 → ACNP
Volume
45
Issue
8
Year of publication
2000
Pages
1517 - 1524
Database
ISI
SICI code
0163-2116(200008)45:8<1517:AOGP(A>2.0.ZU;2-#
Abstract
We investigated possible impairment of the signal transduction system in ga stric myocytes of streptozotocin-induced diabetic (STZ) and spontaneous dia betic WBN/Kob (WBN/Kob) rats. Gastric motility 10 weeks after the onset of diabetes mellitus was significantly reduced in both diabetic rats compared with control, and the decreased motility was not recovered by the administr ation of insulin to maintain normal blood glucose levels. There was no sign ificant difference between both types of diabetic rats and control rats in total number of [H-3]quinuclidinyl benzilate ([H-3]QNB) binding sites (B-ma x: 545-587 fmol/mg protein) on gastric smooth muscle cell membranes or in t he affinity of [H-3]QNB for the binding sites (K-d: 0.06-0.07 nM). Immunobl ot analysis using polyclonal anti-G-protein antibodies indicated increased expression of G(s alpha) in gastric smooth muscle cell membranes, but no si gnificant change in G(i alpha) or G(q/11 alpha) expression in STZ rats, and decreased expression of G(q/11 alpha) with no significant change in G(s al pha) and G(i alpha) in WBN/Kob rats. The cAMP production in gastric smooth muscle cell membranes was augmented in the absence and presence of 100 mu M isoproterenol, and 100 mu M forskolin in STZ rats, whereas no significant change of cAMP production was observed in WBN/Kob rats irrespective of the presence of the stimulants. These findings suggest that long-standing diabe tes may induce alterations in signal transduction at downstream receptors i n gastric myocytes, resulting in the impairment of gastric motility, althou gh the mechanism of reduced contractile activity may differ between STZ and WBN/Kob rats.