Lansoprazole/Naproxen

Cardiac L-type Ca2+ channels are multisubunit complexes composed of alpha 1C, alpha 2 delta, and beta 2 subunits. We tested the roles of these subunits in forming a functional complex by characterizing the effects of subunit composition on dihydropyridine binding, its allosteric regulation, and the ability of dihydropyridines to inhibit channel activity. Transfection of COS.M6 cells with cardiac alpha 1C-a (alpha 1) led to the appearance of dihydropyridine ([3H]PN200-110) binding which was increased by coexpression of cardiac beta 2a (beta), alpha 2 delta a (alpha 2), and the skeletal muscle gamma. Maximum binding was achieved when cells expressed alpha 1, beta, and alpha 2. Cells transfected with alpha 1 and beta had a binding affinity that was 5-10-fold lower than that observed in cardiac membranes. Coexpression of alpha 2 normalized this affinity. (-)-D600 and diltiazem both partially inhibited PN200-100 binding to cardiac microsomes, but stimulated binding in cells transfected with alpha 1 and beta. Again, coexpression of alpha 2 normalized this allosteric regulation. Therefore coexpression of alpha 1 beta and alpha 2 completely reconstituted high affinity dihydropyridine binding and its allosteric regulation as observed in cardiac membranes. Skeletal muscle gamma was not required for this reconstitution. Expression in Xenopus oocytes demonstrated that coexpression of alpha 2 with alpha 1 beta increased the potency and maximum extent of block of Ca2+ channel currents by nisoldipine, a dihydropyridine Ca2+ channel antagonist. Our results demonstrate that alpha 2 subunits are essential components of the cardiac L-type Ca2+ channel and predict a minimum subunit composition of alpha 1C beta 2 alpha 2 delta for this channel.

We wanted to determine what happens to brain PCr and ATP relative to that in liver during a series of dietary manipulation consisting of a severe fast, during eating (when nutrients are intermittently supplied), and during and after PN-100, when an excess amount of nutrients are continuously supplied, using 31P-NMR spectroscopy, in rats randomized to a Fast or Fed group in which energy was provided either as chow or as PN-100. Liver ATP concentration, and brain and liver 31P-nuclear magnetic resonance (NMR) spectras were measured serially. Brain energy metabolism was not different between groups and among days. In contrast, Fasted group showed increased liver ATP/Pi ratio and decreased ATP concentration and ATP/phosphomonoester ratio, there being no difference between Fed and PN-100 groups. Data suggest that brain energy metabolism is maintained regardless of whether energy is supplied intermittently or continuously, and during a negative caloric intake period, brain energy metabolism is quantitatively preserved, suggesting that ATP production by liver is subservient to brain ATP state.