PubMed · 4356549
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L L Iversen. 1973. Catecholamine uptake processes.. https://doi.org/10.1093/oxfordjournals.bmb.a070982
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We recently reported that prostaglandin E2 (PGE2) and arachidonic acid (AA) each induced a gradual secretion of catecholamines from cultured bovine adrenal chromaffin cells in the presence of ouabain by stimulation of phosphoinositide metabolism. In the present study, we examined the relationship between phospholipase A2 and C activation and catecholamine secretion by PGE2 in chromaffin cells. The phospholipase A2 inhibitors p-bromophenacyl bromide and mepacrine did not affect the basal and ouabain-induced release, but dose-dependently blocked PGE2-evoked phosphoinositide metabolism and the consequent catecholamine release at an IC50 value of 3 microM. PGE2 induced rapid hydrolysis of [3H]AA from prelabeled phospholipid pools: the release of [3H]AA could be detected at as early as 15 sec and reached a plateau after 1 min. While the phospholipase C inhibitor neomycin did not inhibit PGE2-induced AA release, phospholipase A2 inhibitors dose-dependently inhibited it at IC50 values comparable to those for catecholamine release. Pretreatment of intact cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, but not with pertussis toxin, prevented AA release by PGE2. These results demonstrate that PGE2 activates phospholipase A2 as well as phospholipase C in a pertussis toxin-insensitive manner and suggest that the released arachidonic acid may be involved in PGE2-induced catecholamine release from chromaffin cells.
How flunarizine, a class IV Ca2+ antagonist, affects the secretion of catecholamines in response to nicotinic receptor activation (10-s pulses with 100 microM dimethylphenylpiperazinium, DMPP) or direct depolarization of chromaffin cells (10-s pulses with 100 mM K+ and 2.5 mM Ca2+, 100 K+/2.5 Ca2+) was studied in bovine adrenal glands perfused with an oxygenated Krebs-Tris solution at 37 degrees C at a rate of 20 ml/min. Experimental protocols aimed to test voltage and time dependence of the flunarizine blocking effects on secretion are described. The DMPP pulses released an average of 217 micrograms catecholamines and the K+ pulses, an average of 117 micrograms. These responses were blocked by flunarizine concentration dependently; IC50s were 3.7 microM for DMPP and 1.1 microM for K+. Under polarizing conditions (60-s perfusion with a solution containing 5.9 mM K+ and nominally zero Ca2+), a 10-s pulse with 100 K+/2.5 Ca2+ released 117 +/- 26 micrograms of catecholamines (n = 12). Under depolarizing conditions (60-s perfusion with 118 K+/0 Ca2+ prior to the Ca2+ pulse), the pulse with 118 K+/2.5 Ca2+ released 307 +/- 36 micrograms of catecholamines (n = 14). Flunarizine blocked these secretory responses equally and concentration dependently with an IC50 of 3.4 microM under polarizing conditions and of 3.8 microM under depolarizing conditions. Thus, blockade by flunarizine of secretion was apparently not voltage-dependent. The blockade was, however, clearly dependent on the time of exposure of the adrenal medullary tissue to flunarizine.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicotinic alpha-bungarotoxin (alpha-BGT) receptors in cultured chromaffin cells are up-regulated in response to long term (days) exposure to nicotinic antagonists, elevated K+, and activators of protein kinase C (PKC), such as the phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA). The present experiments were done to determine whether their was any interaction in the ability of PMA and K+ to up-regulate the alpha-BGT receptors. Chromaffin cells were treated for 3 days with both 100 nM PMA and 20 mM K+, concentrations which produce maximal responses on their own. The increase in alpha-BGT binding after the combined treatment was the same as that seen with K+ alone suggesting that K+ inhibited the PMA-mediated effect. The K(+)-induced increase in toxin binding was partially prevented by polymyxin B, an agent which completely inhibited the PMA induced increase. The time courses of the increases in binding induced by both K+ and PMA were similar in that the most marked increases in binding were observed at the later time points. The PMA-induced up-regulation was partially inhibited by an activator of adenylate cyclase, a result similar to that previously seen with K+. The present studies suggest that the up-regulation of alpha-BGT receptors induced by K+ shares similarities with that induced by phorbol esters. The observations that K+ inhibited the PMA induced increase and that a PKC inhibitor partially blocked the K+ response suggest that the K+ and PMA mediated induction of the alpha-BGT sites may be linked with the effects of K+ preceding those of PMA.