Effects of McN-6186 on voltage-dependent Ca++ channels in heart and pituitary cells.
McN-6186 (N-[2-(3,5-dimethoxyphenyl)ethyl]-5-methoxy-alpha-methyl-2 -(phenylethynyl) benzeneethanamine hydrochloride is a compound structurally distinct from other Ca++ channel ligands. McN-6186 showed some stimulation of 1,4-dihydropyridine-sensitive Ca++ uptake in neonatal rat ventricular cells at concentrations of 1 and 3 nM. At higher concentrations McN-6186 inhibited this uptake in rat ventricular cells at concentrations approximately 100-fold less than those needed to block the corresponding Ca++ uptake in rat anterior pituitary (GH3) cells. McN-6186 (2 microM) inhibited L-type Ca++ channel current in neonatal rat ventricular cells in a voltage-dependent manner while having little or no effect on this current in GH3 cells. In some ventricular cells tested, the T-type Ca++ current was also blocked by 2 microM McN-6186. McN-6186 inhibited (+)-[3H]PN200-110 binding in rat cardiac membranes with an IC50 value of 1.45 X 10(-7) M and a shallow Hill slope (nH = 0.42). It is concluded that McN-6186 blocks L-type Ca++ channels in heart cells preferentially to those found in GH3 cells. Furthermore, McN-6186 may have other sites and mechanisms of action in addition to L-type Ca++ channel blockade.
Rampe
D
D
Department of Physiology & Molecular Biophysics, Baylor College of Medicine, Houston.
Skattebøl
A
A
Triggle
D J
DJ
Brown
A M
AM
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D017275:Isradipine; D008564:Membrane Potentials / Q000187:drug effects; D010069:Oxadiazoles / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D014407:Tumor Cells, Cultured
D000662:Amphetamines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010069:Oxadiazoles; C058409:McN 6186; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D001464:Barium; D002118:Calcium; D017275:Isradipine