Characterization of the binding of [3H]SR 33805 to the slow Ca2+ channel in rat heart sarcolemmal membrane

Biochemical and Pharmacological Properties of SR 33805, a Novel Ca2+ Channel Antagonist

“…The hypothesis that the interaction between fantofarone and SR 33805 is competitive is reinforced by (i) studies showing that fantofarone has no effect on the [3H]SR 33805 rate of dissociation and (ii) [3H]SR 33805 saturation experiments performed in the absence or presence of increasing concentrations of fantofarone. In these studies, B, , , were not modified and K, values were decreased (12). The same conclusion was reached when [3H]fantofarone and unlabelled SR 33805 were used in the same experimental protocols amines, and benzothiazepines) were displaced in a noncompetitive manner by SR 33805 (1 1).…”

“…Other investigations have defined this activity further. In rat cardiac sarcolemmal membranes (12), [3H]SR 33805 bound to a single site with high affinity (Kd = 20 pM). The binding was rapid and reversible.…”

“…2) indicates that only fantofarone inhibits completely 13H]SR 33805 binding with a Hill coefficient of 1, which suggests competitive inhibition. Dihydropyridines, phenylalkylamines, benzothiazepines, and diphenylbutylpiperidines produce only partial inhibition with a Hill coefficient lower than 1, which suggests a noncompetitive interaction (12). The hypothesis that the interaction between fantofarone and SR 33805 is competitive is reinforced by (i) studies showing that fantofarone has no effect on the [3H]SR 33805 rate of dissociation and (ii) [3H]SR 33805 saturation experiments performed in the absence or presence of increasing concentrations of fantofarone.…”

SR33805, a Ca2+ antagonist with length‐dependent Ca2+‐sensitizing properties in cardiac myocytes

“…It has several distinct and important differences, and in vivo studies have shown that SR33805 possesses a different profile of activity in terms of contractile activity compared with fantofarone and other Ca 2+ channel blockers (Chatelain et al ., 1993). This compound binds to alph a 1 ‐subunit of the L‐type Ca 2+ channels with a high affinity ( K D value=20 p M ), but at a site different from the binding site of the classical Ca 2+ channel blockers (Chatelain et al ., 1994). It potently inhibits the Ca 2+ channel in mouse cardiac myocytes in primary culture with IC 50 ranging from 4.1 to 33 n M (Romey et al ., 1994).…”

Alteration of the [Ca2+]i‐force relationship during the vasorelaxation induced by a Ca2+ channel blocker SR33805 in the porcine coronary artery

“…This compound binds to the α 1 subunit of the L‐type Ca 2+ channels, but at a site different from the binding site of the classical Ca 2+ channel blockers ( Melliti et al ., 1996 ; Romey & Lazdunski, 1994 ). It binds with a high affinity ( K D value=20 p M ) to a unique site of the rat cardiac plasma membrane ( Chatelain et al ., 1994 ), and potently inhibits the Ca 2+ channel in the mouse cardiac myocytes in primary culture with IC 50 being 4.1–33 n M ( Romey et al ., 1994 ). Another study demonstrated that SR33805 totally blocked the L‐type Ca 2+ channel with IC 50 being 26 n M in chick dorsal root ganglion neurones ( Romey & Lazdunski, 1994 ).…”