Voltage-dependence of nitrendipine provides direct evidence for dihydropyridine receptor coupling to calcium channels in intact cat adrenals.
Nitrendipine behaves as a powerful inhibitor of catecholamine release in perfused cat adrenal glands stimulated with pulses of Ca (0.5 mM) in high K (118 mM). Its blocking ability is considerably enhanced if, before Ca stimulation, the adrenomedullary tissue is impregnated with nitrendipine in depolarizing (IC50 = 0.99 nM) as opposed to hyperpolarizing (IC50 = 214 nM) conditions. 3H-nitrendipine binding to adrenomedullary tissue was considerably enhanced in depolarization; blockade of 45Ca uptake into and catecholamine secretion from the same glands was also enhanced in depolarized tissues. This study shows for the first time the a good correlation between these three parameters in the same intact preparation, providing direct evidence for a functional coupling between dihydropyridine receptors, Ca channels and secretion.
Artalejo
C R
CR
Departamento de Farmacología, Universidad Autónoma de Madrid, Facultad de Medicina, Spain.
López
M G
MG
Moro
M A
MA
Castillo
C F
CF
de Pascual
R
R
García
A G
AG
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002395:Catecholamines / Q000378:metabolism; D002415:Cats; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials; D009568:Nitrendipine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*
D015220:Calcium Channels; D002395:Catecholamines; D007473:Ion Channels; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D002118:Calcium