Influence of omega-Conotoxin GVIA, Nifedipine and Cilnidipine on Catecholamine Release in the Rat Adrenal Medulla

The present study was designed to establish comparatively the inhibitory effects of cilnidipine (CNP), nifedipine (NIF), and omega-conotoxin GVIA (CTX) on the release of CA evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. CNP (3 micrometer), NIF (3 micrometer), and CTX (3 micrometer) perfused into an adrenal vein for 60 min produced greatly inhibition in CA secretory responses evoked by ACh (5.32 x 10(-3) M), DMPP (10(-4) M for 2 min), McN-A-343 (10(-4) M for 2 min), high K+ (5.6 x 10(-2) M), Bay-K-8644 (10(-5) M), and cyclopiazonic acid (10(-5) M), respectively. For the CA release evoked by ACh and Bay-K-8644, the following rank order of potency was obtained: CNP > NIF > CTX. The rank order for the CA release evoked by McN-A-343 and cyclopiazonic acid was CNP > NIF > CTX. Also, the rank orders for high K+ and for DMPP were NIF > CTX > CNP and NIF > CNP > CTX, respectively. Taken together, these results demonstrate that all voltage-dependent Ca2+ channels (VDCCs) blockers of cilnidipine, nifedipine, and omega-conotoxin GVIA inhibit greatly the CA release evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization without affecting the basal release from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effects of cilnidipine, nifedipine, and omega-conotoxin GVIA are mediated by the blockade of both L- and N-type, L-type only, and N-type only VDCCs located on the rat adrenomedullary chromaffin cells, respectively, which are relevant to Ca2+ mobilization. It is also suggested that N-type VDCCs play an important role in the rat adrenomedullary CA secretion, in addition to L-type VDCCs.

Effects of S-nitrosocaptopril on cyclopiazonic acid-induced [Ca~(2+) ]_i change in rat aortic smooth muscle cells / 中国药理学通报

AIM To study the characteristics of Ca 2+ channel mediated store operated Ca 2+ influx on rat vascular smooth muscle. METHOD Fura 2 fluorescence technique was used to investigate the [Ca 2+ ] i change. RESULTS ① S nitrosocaptopril (CapNO,20～120 ?mol?L -1 ) produced a concentration dependent inhibitory effect on cyclopiazonic acid(CPA) induced [Ca 2+ ] i change. The maximal inhibitory effect(37%?17%) of CapNO was reached at a concentration of 80 ?mol?L -1 . The same concentration of Captopril had no effects. ② Inhibition rate of 80 ?mol?L -1 CapNO (The concentration of maximal effect, CME) on CPA induced [Ca 2+ ] i change was 30%?10%, subsequent addition of 1 ?mol?L -1 Nif (CME)did not further produced the decrease effect (54%?18%). subsequent addition of 20 ?mol?L -1 SK&F96365 (CME) further produced the decrease effect. The inhibitory effects of 20 ?mol?L -1 SK&F96365 were significantly different in the cases of CapNO and Nif pretreatment(24%?10%) and non treatment (54%?11%). ③ The inhibitory effects of 2 ?mol?L -1 tyrphostinAG490(AG490,CME) were significantly different in the cases of CapNO (CME) pretreatment (24%?9%)and non treatment (42%?10%). 80 ?mol?L -1 CapNO effect on CPA induced [Ca 2+ ] i changes in AG490 pretreatment condition(18%?7%) was different from that in non treatment case(37%?10%). CONCLUSION S nitrosocaptopril obviously inhibits the opening of SOCC and VDCC, which mediates store operated Ca 2+ influx. The inhibitory effects of CapNO is associated with both sensitive to and non sensitive to tyrosine kinase (Janus2).