Physiological Role of Calcium Efflux from Neuronal Cells and Its Regulation by Drugs

In adrenal chromaffin cells， which are regarded as model catecholamine-containing neurons and are useful for studies on the Mechanism of stimulus-secretion coupling， secretory stimulation causes an increase in the intracellular free Ca y D12+ y D1 （[Ca y D12+ y D1]i） level originating from intracellular pools and extracellular spaces， leading to catecholamine secretion and activation of catecholamine biosynthesis。After stimulation， the increased [CaイイD12+イエD1]i should rapidly return to the resting level for response to a subsequent stimulation。Opiate peptides such as enkephalins are thought to be stored in the secretory vesicles in the cells， and are co-secreted with catecholamine in response to decreasing the elevated [Cay D12+ y D1]i in adrenal chromaffin cells after physiological stimulation。在这个研究中，我们研究了这个分解在提升[Ca-y D12+ y-D1]i并研究了Ca-y D12+ y-D1 efflux from bovine adrenal chromaffin cells in culture. leucine-and methionine-enkephalin， opiate peptides， on Ca-y D12 + y-y-D1 efflux from cultured bovine adrenal chromaffin cells were examined。These enkephalins stimulated the effManagement of D145 D1Ca D12+ D1 from cells in a concentration-dependent manner （10 D1-8 D1M - 10 D1-6 D1M）。Leucine-enkephalin did not increase the [CaイイD12+イエD1]i，イD145イイD12+イエD1 uptake， catecholamine secretion， CAMP Level or cGMP Level。peptide-stimulated型D145型D1Ca型D12+型D1 effManagement was not inhibited by incubation in Ca型D12+型D1-free medium， but was inhibited by incubation in Na型D1+型D1-free medium。These results indicate that enkephalins stimulate extracellular NaイイD1+イイD1-dependentイD145イイD1CaイイD12+イエD1eff\from cultured bovine adrenal chromaffin cells，Oracle ly by stimulating·brane NaイイD1+イイD1/CaイD12+イエD1 exchange。那么，新的化合物有什么刺激效应的Ca-D12 + E-D1效应可能会被诱导反超敏感效应。

In adrenal chromaffin cells, which are regarded as model catecholamine-containing neurons and are useful for studies on the mechanism of stimulus-secretion coupling, secretory stimulation causes an increase in the intracellular free CaィイD12+ィエD1 ([CaィイD12+ィエD1]i) level originating from intracellular pools and extracellular spaces, leading to catecholamine secretion and activation of catecholamine biosynthesis. After stimulation, the increased [CaィイD12+ィエD1]i should rapidly return to the resting level for response to a subsequent stimulation. Opiate peptides such as enkephalins are thought to be stored in the secretory vesicles in the cells, and are co-secreted with catecholamines in response to decreasing the elevated [CaィイD12+ィエD1]i in adrenal chromaffin cells after physiological stimulation. In this study, we investigated the mechanism of this decrease in elevated [CaィイD12+ィエD1]i and examined the effects of enkephalins on CaィイD12+ィエD1 efflux from bovine adrenal chromaffin cells in culture.The effects of leucine- and methionine-enkephalin, opiate peptides, on CaィイD12+ィエD1 efflux from cultured bovine adrenal chromaffin cells were examined. These enkephalins stimulated the efflux of ィイD145ィエD1CaィイD12+ィエD1 from cells in a concentration-dependent manner (10ィイD1-8ィエD1M - 10ィイD1-6ィエD1M). Leucine-enkephalin did not increase the [CaィイD12+ィエD1]i, ィイD145ィエD1CaィイD12+ィエD1 uptake, catecholamine secretion, CAMP Level or cGMP Level. The peptide-stimulated ィイD145ィエD1CaィイD12+ィエD1 efflux was not inhibited by incubation in CaィイD12+ィエD1-free medium, but was inhibited by incubation in NaィイD1+ィエD1-free medium. These results indicate that enkephalins stimulate extracellular NaィイD1+ィエD1-dependent ィイD145ィエD1CaィイD12+ィエD1 efflux from cultured bovine adrenal chromaffin cells, probably by stimulating membrane NaィイD1+ィエD1/CaィイD12+ィエD1 exchange. Thus, new compounds which have the stimulatory effects of CaィイD12+ィエD1 efflux may indicate anti-hypertensive effects.