Reversal of multidrug resistance in Friend leukemia cells by dexniguldipine-HCl.

Dexniguldipine-HCl (DNIG)--a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MDR)--was evaluated in a drug-accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR), or mitoxantrone (MITO) in resistant F4-6RADR cells to the very levels observed in drug-sensitive F4-6 precursor cells. In parallel with the increase in DNR content (F4-6RADR, solvent: 303 +/- 27 pmol/mg protein; DNIG (3.

Stimulation of bile acid active transport related to increased mucosal cyclic AMP content in rat ileum in vitro.

The regulation of bile acid transport in rat ileum was studied in vitro using the adenylate cyclase stimulator forskolin, or 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. Forskolin 20 microM as well as 100 microM IBMX enhanced mucosal cyclic AMP to 3-fold the control levels. As a physiological response, net fluid absorption in everted ileal sacs was reduced.

Proabsorptive properties of forskolin: disposition of glycine, leucine and lysine in rat jejunum.

The effects of forskolin on mucosal cyclic AMP levels and active transport of glycine, L-lysine and L-leucine were studied in rat jejunum in vitro. Furthermore, the effects on lysine and glycine incorporation into mucosal protein and on mucosal cell volume were investigated. Elevation of intestinal mucosal cyclic AMP to threefold control levels by 10 mumol 1(-1) forskolin was accompanied by increased absorption of glycine (+33%), L-leucine (+72%) and L-lysine (+188%), as determined in a three compartment model suitable to measure active transport.

Response of rat small intestinal active aldohexose transport to elevation of mucosal cyclic AMP by forskolin and 3-isobutyl-1-methylxanthine in vitro.

The phosphodiesterase-inhibitor 3-isobutyl-1-methylxanthine (IBMX) was able to elevate rat small intestinal cyclic AMP levels to 300% of basal values. Active jejunal D-glucose transport was enhanced parallel to the rise of intracellular cyclic AMP levels to 140% of control values at 100 mumol/l IBMX. Transport parameters, as determined in a three compartment model in vitro using a dual label method, indicate increased 'uphill' glucose transport at the site of the brush border membrane, higher intracellular accumulation of the sugar, with unchanged passive permeabilities.