Fig. 12.

Inhibition of T- and L-type channels and cortisol secretion by diphenylbutylpiperidine antagonists. A–D: inhibition of Ca²⁺ currents. Whole cell Ca²⁺ channel currents were recorded from AZF cells in response to voltage steps applied at 30-s intervals from a holding potential of −80 mV. Cells were superfused with pimozide (A), penfluridol (B and C), and fluspirilene (D). External solution contained 10 mM Ca²⁺ (A and B) and 10 mM Ba²⁺ (C and D). Numbers on traces in C and D correspond to initial currents (1), maximum control currents (2), and current after block by penfluridol or fluspirilene (3). E: inhibition of ACTH-stimulated cortisol secretion. At 24 h after bovine AZF cells were plated, medium was aspirated and replaced with defined medium without (control) or with ACTH (2 nM), alone or in combination with TTA-P2, nifedipine, niguldipine (Nigul), penfluridol (Penfl), pimozide (Pimoz), or fluspirilene (Flusp), each at 2 μM. Antagonist (Antag)-treated cells were preexposed to that agent for 30 min prior to addition of ACTH. Medium was collected at 2 h and 24 h, and cortisol was measured. Values are means ± SE of duplicate determinations from triplicate plates. P < 0.002 for each antagonist at 2 and 24 h compared with ACTH-stimulated value.