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Chemical Compound Review

BAY-K-8644     methyl 2,6-dimethyl-5-nitro-4-[2...

Synonyms: BayK8644, SureCN133106, B112_SIGMA, AG-J-73150, BAY-R 4407, ...
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Disease relevance of Bay K 8644


Psychiatry related information on Bay K 8644


High impact information on Bay K 8644

  • Recently, small modifications to the nifedipine molecule produced a derivative, BAY-K-8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate), that in contrast to the Ca2+-channel blocking agents, stimulated cardiac and vascular smooth muscle contractility [6].
  • Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels [6].
  • Quantitative PCR analysis showed that stimulation with high concentration of KCl, BAY-K 8644, or 12-O-tetradecanoyl phorbol-13-acetate resulted in an immediate and substantial increase (two- to threefold) of Kv1.4 mRNA levels in spontaneously beating myocytes prepared from neonatal rat ventricles [7].
  • In excised, inside-out patches, Po was low spontaneously and remained low during either bath protein kinase A catalytic subunit (PKAcs) or Bay K 8644 [8].
  • In comparison with P-type Ca2+ channels in rat cerebellar Purkinje cells, alpha 1A channels in oocytes are approximately 10(2)-fold less sensitive to omega-Aga-IVA and approximately 10-fold more sensitive to omega-CTx-MVIIC. alpha 1A channels are not inhibited by Bay K 8644 and inactivate much more rapidly than P-type Ca2+ channels [9].

Chemical compound and disease context of Bay K 8644


Biological context of Bay K 8644

  • In contrast, Bay K 8644 (10(-7) M), a calcium-channel agonist, exacerbated ischemia-induced conduction slowing and depression of Vmax but did not significantly affect resting membrane potential [14].
  • BAY K 8644 did not activate nonphosphorylated channels, and (+)-PN200-110 caused dramatic prolongation of mean open times when applied after phosphorylation [15].
  • The mechanism of drug action was evaluated by measuring the effects of Bay k 8644 on twitch tension, action potential configuration, and calcium channel currents in myocardial cells [16].
  • These data suggest that binding of Bay k 8644 to high affinity binding sites is pharmacologically relevant, and is related to a positive inotropic effect [17].
  • However, either the voltage-dependent properties or the dose-response relationships of Bay K 8644- and second messenger-induced modulations of L-type Ca2+ current did not differ in the four phases of the cell cycle [18].

Anatomical context of Bay K 8644

  • Thus, physical contact between a sympathetic neuron and previously uninnervated neonatal rat ventricular myocytes increases expression of functional L-type calcium channels as judged by contractile responses to Ca0 and Bay K 8644, as well as by electrophysiological and radioligand binding properties [19].
  • Increasing the perfusate calcium or use of the calcium channel agonist, BAY-K 8644, increased cytosolic calcium to near maximum but had little effect on contractility, confirming that the relationship between calcium and the myofilaments had been altered [20].
  • Moreover, increased efficacy of Bay K 8644 was maintained for at least 24 h after denervation produced by removal of ganglia from the culture [19].
  • PC12 cells were cultured on monolayers of control 3T3 cells or 3T3 cells expressing transfected N-cadherin in the presence of KCl or a calcium channel agonist Bay K 8644 [21].
  • No effect of Bay K 8644 was observed in synaptosomes isolated from brainstem [22].

Associations of Bay K 8644 with other chemical compounds

  • The (-) isomer of Bay K 8644 and the (+) isomer of Sandoz compound 202-791 were 100-1000 times more potent than their respective opposite enantiomers in enhancing Ca2+ uptake and dopamine release from striatal synaptosomes [22].
  • In both myocyte preparations, Bay K 8644 increased the rate of 45Ca uptake by 25% at 60 seconds; verapamil decreased 45Ca uptake at 60 seconds by 16% and 17% in normal and CM hamsters, respectively [23].
  • The cardiac output (CO) of control hearts recovered to 74.7 +/- 3.4%, whereas recovery was 56.3 +/- 3.7% (p less than 0.05) for high calcium (10 mM), 53.4 +/- 3.6% (p less than 0.05) for isoproterenol, 43.4 +/- 4.1% (p less than 0.05) for Bay K 8644, and 62.7 +/- 2.4% (p less than 0.002) for forskolin [24].
  • Endothelin (10(-7) M, +61%), 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-6) M, +62%), the calcium ionophore A23187 (10(-6) M, +95%), and Bay K 8644 (10(-6) M, +34%) (p < 0.05 each) all increased the secretion of ANP into the culture media in a dose-dependent fashion [25].
  • In Purkinje fibers, APD alternans was attenuated by a Ca2+ channel blocker, nisoldipine (2 X 10(-6) M), and augmented by a Ca2+ channel agonist, Bay K 8644 (3 X 10(-8) M) [26].

Gene context of Bay K 8644

  • SRIF (10 nM) completely blocks the stimulatory effects of 1 microM Bay K 8644 and markedly inhibits the effects of 50 mM KCl from as early as the ninth week of fetal age [27].
  • The calcium channel activator Bay K 8644 stimulated a 3-fold increase in Ca/CaMK II activity, similar to GnRH [28].
  • However, 1-h stimulation by AVP or activation of calcium channels (by Bay K 8644) or protein kinase-C by 12-O-tetradecanoyl-phorbol-13-acetate did not restore CRH binding [29].
  • (-)-3-PPP tended to reduce the PRL release induced by the Ca2+ channel agonist BAY K-8644 (BAY); however, this effect of the partial agonist was modest and not significant [30].
  • The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644 [31].

Analytical, diagnostic and therapeutic context of Bay K 8644


  1. Reduced L-type calcium current in the embryonic chick heart with persistent truncus arteriosus. Creazzo, T.L. Circ. Res. (1990) [Pubmed]
  2. Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart: mechanism and characteristics of steady contractile activation in intact myocardium. Marban, E., Kusuoka, H., Yue, D.T., Weisfeldt, M.L., Wier, W.G. Circ. Res. (1986) [Pubmed]
  3. G protein specificity in receptor-effector coupling. Analysis of the roles of G0 and Gi2 in GH4C1 pituitary cells. Liu, Y.F., Jakobs, K.H., Rasenick, M.M., Albert, P.R. J. Biol. Chem. (1994) [Pubmed]
  4. Canine left ventricular hypertrophy predisposes to ventricular tachycardia induction by phase 2 early afterdepolarizations after administration of BAY K 8644. Ben-David, J., Zipes, D.P., Ayers, G.M., Pride, H.P. J. Am. Coll. Cardiol. (1992) [Pubmed]
  5. Inhibitory effects of D2 agonists by striatal injection on excessive release of dopamine and hyperactivity induced by Bay K 8644 in rats. Maruya, H., Watanabe, Y., Okita, M., Lawlor, G.F., Utsumi, H., Niitsuma, T. Neuroscience (2003) [Pubmed]
  6. Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels. García, A.G., Sala, F., Reig, J.A., Viniegra, S., Frías, J., Fontériz, R., Gandía, L. Nature (1984) [Pubmed]
  7. Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy. Matsubara, H., Suzuki, J., Inada, M. J. Clin. Invest. (1993) [Pubmed]
  8. Patch-clamp evidence for calcium channels in apical membranes of rabbit kidney connecting tubules. Tan, S., Lau, K. J. Clin. Invest. (1993) [Pubmed]
  9. Distinctive biophysical and pharmacological properties of class A (BI) calcium channel alpha 1 subunits. Sather, W.A., Tanabe, T., Zhang, J.F., Mori, Y., Adams, M.E., Tsien, R.W. Neuron (1993) [Pubmed]
  10. Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats. Laurent, S., Girerd, X., Tsoukaris-Kupfer, D., Legrand, M., Huchet-Brisac, A.M., Schmitt, H. Hypertension (1987) [Pubmed]
  11. 45Ca uptake and the actions of Bay K 8644 on aortic strips from rabbits with perinephritis hypertension. Dong, Y., Wadsworth, R.M. J. Hypertens. (1987) [Pubmed]
  12. Dihydropyridine modulation of voltage-activated calcium channels in PC12 cells: effect of pertussis toxin pretreatment. Schettini, G., Meucci, O., Grimaldi, M., Florio, T., Landolfi, E., Scorziello, A., Ventra, C. J. Neurochem. (1991) [Pubmed]
  13. Rhythm anomalies related to delayed repolarization in vivo: influence of sarcolemmal Ca++ entry and intracellular Ca++ overload. Carlsson, L., Drews, L., Duker, G. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  14. Modulation of conduction slowing in ischemic rabbit myocardium by calcium-channel activation and blockade. Kabell, G. Circulation (1988) [Pubmed]
  15. Purified skeletal muscle 1,4-dihydropyridine receptor forms phosphorylation-dependent oligomeric calcium channels in planar bilayers. Hymel, L., Striessnig, J., Glossmann, H., Schindler, H. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  16. A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent. Thomas, G., Chung, M., Cohen, C.J. Circ. Res. (1985) [Pubmed]
  17. Effects of Bay k 8644, a dihydropyridine analog, on [3H]nitrendipine binding to canine cardiac sarcolemma and the relationship to a positive inotropic effect. Vaghy, P.L., Grupp, I.L., Grupp, G., Schwartz, A. Circ. Res. (1984) [Pubmed]
  18. Cell cycle--dependent expression of L- and T-type Ca2+ currents in rat aortic smooth muscle cells in primary culture. Kuga, T., Kobayashi, S., Hirakawa, Y., Kanaide, H., Takeshita, A. Circ. Res. (1996) [Pubmed]
  19. Direct contact between sympathetic neurons and rat cardiac myocytes in vitro increases expression of functional calcium channels. Ogawa, S., Barnett, J.V., Sen, L., Galper, J.B., Smith, T.W., Marsh, J.D. J. Clin. Invest. (1992) [Pubmed]
  20. Mechanism of myocardial contractile depression by clinical concentrations of ethanol. A study in ferret papillary muscles. Guarnieri, T., Lakatta, E.G. J. Clin. Invest. (1990) [Pubmed]
  21. Direct activation of second messenger pathways mimics cell adhesion molecule-dependent neurite outgrowth. Saffell, J.L., Walsh, F.S., Doherty, P. J. Cell Biol. (1992) [Pubmed]
  22. Characterization of dihydropyridine-sensitive calcium channels in rat brain synaptosomes. Woodward, J.J., Cook, M.E., Leslie, S.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  23. Inotropic and calcium kinetic effects of calcium channel agonist and antagonist in isolated cardiac myocytes from cardiomyopathic hamsters. Sen, L.Y., O'Neill, M., Marsh, J.D., Smith, T.W. Circ. Res. (1990) [Pubmed]
  24. Modulation of severity of reperfusion stunning in the isolated rat heart by agents altering calcium flux at onset of reperfusion. du Toit, E.F., Opie, L.H. Circ. Res. (1992) [Pubmed]
  25. Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells. Suzuki, E., Hirata, Y., Kohmoto, O., Sugimoto, T., Hayakawa, H., Matsuoka, H., Sugimoto, T., Kojima, M., Kangawa, K., Minamino, N. Circ. Res. (1992) [Pubmed]
  26. Alternans of action potential duration after abrupt shortening of cycle length: differences between dog Purkinje and ventricular muscle fibers. Saitoh, H., Bailey, J.C., Surawicz, B. Circ. Res. (1988) [Pubmed]
  27. In vitro modulation of growth hormone (GH) secretion from early to midgestation human fetal pituitaries by GH-releasing factor and somatostatin: role of Gs-adenylate cyclase-Gi complex and Ca2+ channels. Goodyer, C.G., Branchaud, C.L., Lefebvre, Y. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  28. The calcium component of gonadotropin-releasing hormone-stimulated luteinizing hormone subunit gene transcription is mediated by calcium/calmodulin-dependent protein kinase type II. Haisenleder, D.J., Ferris, H.A., Shupnik, M.A. Endocrinology (2003) [Pubmed]
  29. Rapid corticosterone inhibition of corticotropin-releasing hormone binding and adrenocorticotropin release by enriched populations of corticotropes: counteractions by arginine vasopressin and its second messengers. Childs, G.V., Unabia, G. Endocrinology (1990) [Pubmed]
  30. The intrinsic activity of (-)-3-PPP vis-à-vis prolactin-suppressing dopamine D2 receptors in transfected GH4C1 cells is dependent on which secretagogue that is used to provoke prolactin release. Nilsson, C.L., Hellstrand, M., Ekman, A., Eriksson, E. Neuropharmacology (1998) [Pubmed]
  31. Comparison between the vasoactive actions of endothelin and arginine vasopressin in pithed rats after pretreatment with BAY K 8644, nifedipine or pertussis toxin. Tabrizchi, R., Triggle, C.R. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
  32. Bay K 8644 increases resting Ca2+ spark frequency in ferret ventricular myocytes independent of Ca influx: contrast with caffeine and ryanodine effects. Satoh, H., Katoh, H., Velez, P., Fill, M., Bers, D.M. Circ. Res. (1998) [Pubmed]
  33. Characterization of the electrically evoked release of substance P from dorsal root ganglion neurons: methods and dihydropyridine sensitivity. Holz, G.G., Dunlap, K., Kream, R.M. J. Neurosci. (1988) [Pubmed]
  34. Role of ATP-dependent K(+) channels in the electrical excitability of early embryonic stem cell-derived cardiomyocytes. Gryshchenko, O., Fischer, I.R., Dittrich, M., Viatchenko-Karpinski, S., Soest, J., Böhm-Pinger, M.M., Igelmund, P., Fleischmann, B.K., Hescheler, J. J. Cell. Sci. (1999) [Pubmed]
  35. Contractions of dysgenic skeletal muscle triggered by a potentiated, endogenous calcium current. Adams, B.A., Beam, K.G. J. Gen. Physiol. (1991) [Pubmed]
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