These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Activators of protein kinase A induce a glibenclamide-sensitive 86Rb+ efflux in rat isolated aorta.
    Author: Kessler C, Löffler C, Linde C, Baumlin Y, Quast U.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1997 Apr; 355(4):483-90. PubMed ID: 9109365.
    Abstract:
    The effect of activators of protein kinase A on membrane K+ permeability and the interaction of these compounds with cromakalim, an opener of ATP-sensitive K+ channels (K(ATP) channels), were investigated. Membrane K+ permeability was assessed by measuring 86Rb+ efflux from rings of rat aorta. Forskolin, an activator of adenylate cyclase, and isobutylmethylxanthine (IBMX), a nonselective phosphodiesterase inhibitor, induced small, concentration-dependent increases in tracer efflux up to 20-40% over the basal level. The effect of forskolin was abolished by the K+ channel blocker tedisamil (1 microM) and partially inhibited by glibenclamide (1 microM), a relatively selective blocker of K(ATP) channels. Further studies were conducted in the presence of 35 mM KCI in the bath in order to increase the size of the 86Rb+ efflux stimulated by forskolin and IBMX. At high concentrations, these compounds produced a biphasic effect with a peak increase being followed by a lower plateau value. Glibenclamide inhibited the 86Rb+ efflux response to forskolin and IBMX by 50-80%. The K+ channel blockers tedisamil (1 microM), Ba2+ (1 mM) and tetraethylammonium (10 mM) also reduced the peak response to forskolin by about 50% and abolished or greatly inhibited the plateau response. In addition to the small effect on basal 86Rb+ efflux, forskolin (0.3 microM) increased cromakalim-induced 86Rb+ efflux 3.4 times. At higher concentrations, however, a concentration-dependent inhibition was observed with an IC50 value of 7.6 +/- 0.4 microM. 1,9-dideoxyforskolin, which does not increase cAMP, increased neither basal nor cromakalim-induced 86Rb+ efflux; however, it inhibited cromakalim-stimulated tracer efflux with an IC50 value of 22 +/- 2 microM. It is concluded that forskolin and IBMX, probably by increasing intracellular cAMP levels, induce a 86Rb+ efflux from rat aorta, the major part of which is glibenclamide-sensitive and may pass through K(ATP) channels. In addition, low concentrations of forskolin greatly facilitate the K(ATP) channel opening effect of cromakalim whereas high concentrations block the channel; this blocking effect of forskolin is unrelated to the cAMP elevating action.
    [Abstract] [Full Text] [Related] [New Search]