Influence of staurosporine on catecholamine release evoked by cholinergic stimulation and membrane depolarization from the rat adrenal gland

The present study was attempted to examine the effect of staurosporine (STS) on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal gland and to establish its mechanism of action. The perfusion of STS (3 X 10(-7) ~3 X 10(-8) M) into an adrenal vein for 20 min produced a dose-dependent inhibition in CA secretion evoked by ACh (5.32 X 10(-3) M), high K+ (5.6 X 10(-2) M), DMPP (10(-4) M for 2 min), McN-A-343 (10(-4) M for 2 min), cyclopiazonic acid (10(-5) M for 4 min) and Bay-K-8644 (10(-5) M for 4 min). Also, in the presence of tamoxifen (2 X 10(-6) M), which is known to be a protein kinase inhibitor, CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly depressed. However, in adrenal glands preloaded with STS (10(-7) M) under the presence of phorbol-12,13-dibutyrate (10(-7) M), a specific activator of protein kinases (for 20 min), the inhibitory effect of STS on CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid was greatly recovered to the extent of the control release as compared to those in the presence of STS only. These results demonstrate that STS causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization, indicating strongly that this effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells through preventing activation of protein kinases. Furthermore, these findings also suggest that these STS-sensitive protein kinases play a modulatory role partly in regulating the rat adrenomedullary CA secretion.

Influence of Total Ginseng Saponin on Contractile Responses of Vasoconstrictors in the Isolated Rat Aorta

BACKGROUND: It has been known that Ginseng extract causes the hypotensive action while it rather produces the hypertensive action. Some studies have suggested that Ginseng extract causes a biphasic response on blood pressure, namely, transient fall followed by prolonged elevation. It has been also shown that administration of Korean Red Ginseng powder has no effect on blood pressure in normotensive and hypertensive rats. The present study was designed to examine the effect of total Ginseng saponin on contractile responses of vasoconstrictors in the rat aorta and to establish the mechanism of its action. METHODS: The ring segment of aorta was mounted in a muscle bath filled with oxygenated Krebs solution for the measurement of isometric tension. After the equilibration period, under the presence of total Ginseng saponin, isometric tension induced by some vasoconstrictors were observed and compared to the control responses. The data were expressed as % of the control tension. RESULTS: Phenylephrine (an adrenergic alpha1-receptor agonist) and high potassium (a membrane depolarizing agent) caused greatly contractile responses in the rat aorta, respectively. However, in the presence of total ginseng saponin (600 g/ml), the contractile responses of phenylephrine (10(-6) and 10(-5) M) and high potassium (3.5 x 10(-2) and 5.6 x 10(-2) M) were markedly potentiated whereas prostglandin F2alpha(5 x 10(-6) M)-induced contractile responses was not affected. The contractile responses induced by phenylephrine (10(-5) M) and high potassium (3.5 x 10(-2) M) even under the presence of total ginseng saponin (600 g/ml) were greatly inhibited by the pretreatment of nicardipine (10(-6) M), a calcium channel blocker. CONCLUSION: Taken together, these experimental results suggest that total ginseng saponin can enhance the contractile responses evoked by stimulation of adrenergic alpha1-receptor and the membrane depolarization in the isolated rat aortic strips, which seems to be associated to calcium influx.