cancer is a leading cause of death worldwide. despite the availability of several chemotherapeutic drugs, there is still a great need for more efficient agents for a better management of cancer. in this contribution, a series of 11 dhps (4a, 4b & 7a-i) were synthesized and evaluated for their cytotoxic effect against mcf-7, ls180, and molt-4 cancer cell lines using mtt assay. synthesized 2,6-di...

The deficiency of dystrophin, a critical membrane stabilizing protein, in the mdx mouse causes an elevation in intracellular calcium in myocytes. One mechanism that could elicit increases in intracellular calcium is enhanced influx via the L-type calcium channels. This study investigated the effects of the dihydropyridines BAY K 8644 and nifedipine and alterations in dihydropyridine receptors i...

Voltage-dependent calcium channels play a role in many cellular phenomena. Very little is known about Ca2+ channels in Drosophila, especially those in muscles. Existing literature on neuronal Ca2+ channels of Drosophila suggests that their pharmacology may be distinct from that of vertebrate Ca2+ channels. This raises questions on the pharmacology and diversity of Ca2+ channels in Drosophila mu...

The influx of Ca ions into the presynaptic nerve terminal through ion channels is a key link between the action potential and the release of chemical transmitters. It is not clear, however, which types of Ca channel are involved in neurosecretion at vertebrate synapses. In particular, there is disagreement as to whether these channels are sensitive to dihydropyridine blockers, characteristic of...

Skeletal and cardiac dihydropyridine receptors function both as voltage-dependent L-type calcium channels (L-channels) and as critical proteins that trigger calcium release from the sarcoplasmic reticulum in muscle. In spite of these similarities, skeletal L-channels exhibit a markedly slower activation rate than cardiac L-channels. We investigated the mechanisms underlying this difference by c...

We investigated the mechanism of interaction of individual L-type channel amino acid residues with dihydropyridines within a dihydropyridine-sensitive a1A subunit (a1ADHP). Mutation of individual residues in repeat III and expression in Xenopus oocytes revealed that Thr is not required for dihydropyridine interaction but that bulky side chains (tyrosine, phenylalanine) in this position sterical...

Epilepsy is a chronic disorder of the brain affecting around 50 million people in the world.Up to 30% of epileptic patients do not respond to available drugs and medical therapies. In thispaper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine-3,5-dicarboxamides was performed.Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylenetetr...

We measured [3H]PN200-110 binding and patch-clamp currents in rabbit ventricular myocytes to determine if there is a disparity between the density of dihydropyridine-specific receptors and functional L-type calcium channels, as has been reported for skeletal muscle. The dihydropyridine receptor density was 74.7 +/- 4.2 fmol/mg protein (mean +/- SEM, Kd = 1.73 +/- 0.29 nM, n = 6) in ventricular ...

The subcellular distribution of the 1,4-dihydropyridine receptor was determined in rabbit skeletal muscle in situ by immunofluorescence and immunoelectron microscopy. Longitudinal and transverse cryosections (5-8 microns) of rabbit gracilis muscle were labeled with monoclonal antibodies specific against either the alpha 1-subunit (170,000-D polypeptide) or the beta-subunit (52,000-D polypeptide...