Calmodulin antagonists inhibit dihydropyridine calcium channel activator (BAY-K-8644) induced cGMP synthesis in pituitary tumor cells

1986 ◽  
Vol 64 (6) ◽  
pp. 760-763 ◽  
Author(s):  
Seymour Heisler
Keyword(s):  
Calcium Channel ◽  
Bay K 8644 ◽  
Dependent Manner ◽  
Calmodulin Antagonists ◽  
Concentration Dependent Manner ◽  
Calcium Channel Activator ◽  
Cgmp Formation ◽  
Cgmp Synthesis ◽  
Channel Activator

The dihydropyridine calcium channel activator, BAY-K-8644, stimulates cGMP formation in ACTH-secreting mouse AtT-20 clonal corticotrophs. The recent report that calmodulin antagonists could inhibit dihydropyridine binding in several tissues suggested that these agents might also affect the cyclic nucleotide response to BAY-K-8644. In fact, TMB-8, trifluoperazine, and melittin, described as in vitro antagonists of calmodulin-dependent enzyme activities, all inhibited BAY-K-8644 induced cGMP synthesis in a concentration-dependent manner. The antagonists had no effect on cGMP formation stimulated by sodium nitroprusside or sodium azide. The calcium channel antagonist, nifedipine, did not stimulate cGMP formation nor did it alter the effect of BAY-K-8644 on accumulation of the nucleotide; one explanation thus is that the cyclase involved in cGMP formation is coupled to a low affinity binding site for BAY-K-8644, which is less accessible to other dihydropyridines. The relation of cyclic GMP formation to the function of the calcium channel in AtT-20 cells remains unknown.

In vitro and in vivo vascular responses to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis

1998 ◽  
Vol 13 (12) ◽  
pp. 1254-1258 ◽  
Author(s):  
RICHARD MOREAU ◽  
FREDERIC OBERTI ◽  
PHILIPPE LAHAYE ◽  
ADRIAN GADANO ◽  
STEPHANE CAILMAIL ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Bay K 8644 ◽  
Vascular Responses ◽  
Calcium Channel Activator ◽  
Channel Activator

Involvement of calmodulin in mediating inhibitory action of intracellular Ca2+ on renin secretion

1986 ◽  
Vol 251 (6) ◽  
pp. F1055-F1062 ◽  
Author(s):  
C. S. Park ◽  
T. W. Honeyman ◽  
E. S. Chung ◽  
J. S. Lee ◽  
D. H. Sigmon ◽  
...  
Keyword(s):  
Renin Secretion ◽  
Cell Membrane Permeability ◽  
Dependent Manner ◽  
Calmodulin Antagonists ◽  
Structural Analogue ◽  
Concentration Dependent Manner ◽  
Calmodulin Antagonist ◽  
High K ◽  
Cortical Slices

This study sought to elucidate further the cellular mechanism(s) involved in the control of renin secretion by Ca2+. The rate of renin secretion in vitro by rabbit and dog renal cortical slices was inversely related to medium Ca2+ concentration. The inverse relationship was observed only when the cell membrane permeability to Ca2+ was increased by K+ depolarization, suggesting that the Ca2+ concentration in the juxtaglomerular cell modulates renin secretion. From this relationship, renin secretion appears to turn on at intracellular Ca2+ concentrations between 10(-8) and 10(-7) M. Calmidazolium, a potent calmodulin antagonist, markedly stimulated basal renin secretion in a concentration-dependent manner. Pretreatment of slices with calmidazolium blocked the inhibition of renin secretion by high-K+ medium. Calmidazolium and several other calmodulin antagonists (W-7, W-13, and trifluoperazine) partly or fully reversed the inhibition of renin secretion previously inhibited by high-K+ medium in the order of their potencies as calmodulin antagonists. Indeed, W-5, a biologically inactive structural analogue of W-7, was without effect. These results support the hypothesis that renin secretion is inversely related to intracellular Ca2+ and that Ca2+ inhibits renin secretion by a calmodulin-dependent process.

Effects of the Calcium Channel Activator BAY-K-8644 onin VitroSecretion of Calcitonin and Parathyroid Hormone*

Endocrinology ◽  
1986 ◽  
Vol 118 (2) ◽  
pp. 545-549 ◽  
Author(s):  
CARY W. COOPER ◽  
SUSAN A. BOROSKY ◽  
PATRICK E. FARRELL ◽  
ODD S. STEINSLAND
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Channel ◽  
Bay K 8644 ◽  
Calcium Channel Activator ◽  
Channel Activator

Further investigation of a potential calcium channel modulator isolated from rat erythrocytes

1989 ◽  
Vol 67 (10) ◽  
pp. 1252-1258 ◽  
Author(s):  
Bing S. Huang ◽  
William D. McCumbee ◽  
Gary L. Wright
Keyword(s):  
Calcium Channel ◽  
Contractile Response ◽  
Aortic Ring ◽  
Bay K 8644 ◽  
Aortic Tissue ◽  
Dependent Manner ◽  
Response Curves ◽  
Rat Erythrocytes ◽  
Maximum Enhancement ◽  
Concentration Dependent Manner

The contractile effects of a peptide isolated from rat erythrocytes were further studied in rat aortic rings. Previous data showed that preincubation of aortic tissue with the peptide had no effect on resting tension, but significantly enhanced K+ and norepinephrine (NE) induced contraction. The calcium channel antagonist verapamil noncompetitively blocked the effect of the peptide, whereas nifedipine blockage appeared to be competitive. In the present study the peptide enhanced K+, NE, and phenylephrine (PE) induced contraction in a concentration-dependent manner, with a maximum enhancement at peptide concentrations of 10−7–10−6 M. At a concentration as low as 10−9 M, the peptide significantly enhanced K+-induced, but not NE- or PE-induced, contraction. The magnitude of maximal enhancement was greater for K+-induced contraction than that for NE- or PE-induced contraction. Preincubation of the tissues with the peptide caused a leftward shift of cumulative concentration–response curves to K+ and NE. The peptide enhancement of contraction increased with increasing K+ and NE concentration. The peptide potentiated the contractile response to Ca2+ in K+-depolarizing medium. It also enhanced the contractile response to NE in intracellular Ca2+-pool-depleted tissue following the replenishment of extracellular Ca2+, but had no apparent effect on the mobilization of intracellular calcium. Addition of nifedipine caused a rightward shift of both the peptide and Bay K 8644 concentration–response curves. Schild analysis for nifedipine antagonism, however, showed that the slope of the plot was significantly different from unity in both the Bay K 8644 and peptide responses, invalidating the use of this technique for conclusions regarding the nature of the nifedipine antagonism and site of action of the peptide. These data indicate that this peptide, like Bay K 8644, may influence the contractile sensitivity of aortic smooth muscle by acting as an endogenous modulator of voltage-dependent calcium channels.Key words: peptide, rat aortic ring, contractility, Bay K 8644.

Dimemorfan prevents seizures induced by the L-type calcium channel activator BAY k-8644 in mice

2004 ◽  
Vol 151 (1-2) ◽  
pp. 267-276 ◽  
Author(s):  
Eun-Joo Shin ◽  
Toshitaka Nabeshima ◽  
Phil Ho Lee ◽  
Won-Ki Kim ◽  
Kwang Ho Ko ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Bay K 8644 ◽  
Calcium Channel Activator ◽  
Channel Activator

Central and peripheral effects of the dihydropyridine calcium channel activator BAY K 8644 in the rat

1989 ◽  
Vol 160 (3) ◽  
pp. 339-347 ◽  
Author(s):  
Anne Bourson ◽  
Paul C. Moser ◽  
Alma J. Gower ◽  
Anis K. Mir
Keyword(s):  
Calcium Channel ◽  
Bay K 8644 ◽  
Calcium Channel Activator ◽  
Channel Activator

BAY-K-8644-stimulated amylase secretion from pancreatic acinar cells

1988 ◽  
Vol 66 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Seymour Heisler ◽  
Diane Desjardins ◽  
Marthe Belles-Isles
Keyword(s):  
Calcium Channel ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Secretory Response ◽  
Bay K 8644 ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
Calcium Channel Antagonists ◽  
Calcium Channel Activator ◽  
Cgmp Synthesis

Pancreatic acinar cells do not contain depolarization-sensitive calcium channels. Nonetheless, in the current study, the calcium channel activator, BAY-K-8644, was found to stimulate a time- and concentration-dependent increase in the spontaneous release of amylase. Secretion was dependent on the presence of extracellular calcium in the incubation medium. Racemic BAY-K-8644 and (or) its S(−)optical isomer did not enhance the secretory response to either carbachol or cholecystokinin octapeptide; however, when co-applied with either phorbol ester, vasoactive intestinal peptide, or forskolin, they potentiated amylase secretion. Nifedipine and the R(+)isomer of BAY-K-8644, which are both calcium channel antagonists, did not alter basal or forskolin-stimulated amylase secretion, and [3H]nitrendipine did not bind to acinar cell membranes. Neither atropine nor dibutyryl cGMP, inhibitors of cholinergic and cholecystokininergic receptors, respectively, affected BAY-K-8644-induced amylase secretion. While BAY-K-8644 stimulated concentration-dependent cGMP synthesis in acinar cells, it had no effect on basal or forskolin-stimulated cAMP formation. The data suggest that BAY-K-8644 may bind to acinar cell sites that are not functional calcium channel proteins but are coupled nevertheless to the secretory response, and that calcium channel antagonists do not bind to these sites. The mechanism of the secretagogue action of BAY-K-8644 remains to be elucidated.

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