Calcium Uptake Inhibition Activity

  • Michael Gralinski
  • Liomar A. A. Neves
  • Olga Tiniakova
Living reference work entry


Cellular calcium flux is regulated by receptor-operated and voltage-dependent channels, which are sensitive to inhibition by calcium entry blockers. The term calcium antagonist was introduced by Fleckenstein (1964, 1967) when two drugs, prenylamine and verapamil, originally found as coronary dilators in the Langendorff experiment, were shown to mimic the cardiac effects of simple Ca2+ withdrawal, diminishing Ca2+-dependent high-energy phosphate utilization, contractile force, and oxygen requirement of the beating heart without impairing the Na+-dependent action potential parameters. These effects were clearly distinguishable from β-receptor blockade and could promptly be neutralized by elevated Ca2+, β-adrenergic catecholamines, or cardiac glycosides, measures that restore the Ca2+ supply to the contractile system. In the following years, many Ca2+ antagonists were introduced to therapy. Specific Ca2+ antagonists interfere with the uptake of Ca2+ into the myocardium and prevent myocardial necrotization arising from deleterious intracellular Ca2+ overload. They act basically as specific inhibitors of the slow transsarcolemnal Ca2+ influx but do not or only slightly affect the fast Na+ current that initiates normal myocardial excitation.


Calcium Channel Calcium Antagonist Calcium Channel Antagonist Calcium Entry Blocker Intracellular Action Potential 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Further Reading

General Considerations

  1. Barhanin J, Borsotto M, Coppola T, Fosset M, Hosey MM, Mourre C, Pauron D, Qar J, Romey G, Schmid A, Vandaele S, Van Renterghem C, Lazdunski M (1989) Biochemistry, molecular pharmacology, and functional control of Ca2+-channels. In: Wray DW, Norman RI, Hess P (eds) Calcium channels: structure and function, vol 560, Annals of the New York Academy of Sciences. New York Academy of Sciences, New York, pp 15–26Google Scholar
  2. Bean BP (1989) Classes of calcium channels in vertebrate cells. Annu Rev Physiol 51:367–384PubMedGoogle Scholar
  3. Berjukow S, Marksteiner R, Gapp F, Sinnegger MJ, Hering S (2000) Molecular mechanism of calcium channel block by isradipine. J Biol Chem 275:22114–22120PubMedGoogle Scholar
  4. Bertolino M, Llinás RR (1992) The central role of voltage-activated and receptor-operated calcium channels in neuronal cells. Annu Rev Pharmacol Toxicol 32:399–421PubMedGoogle Scholar
  5. Catterall WA (1998) Receptor sites for blockers of L-type calcium channels. Naunyn-Schmiedeberg’s Arch Pharmacol 358(suppl 2):R 582Google Scholar
  6. Catterall WA, Saegar MJ, Takahashi M, Nunoki K (1989) Molecular properties of dihydropyridine-sensitive calcium channels. In: Wray DW, Norman RI, Hess P (eds) Calcium channels: structure and function, vol 560, Annals of the New York Academy of Sciences. New York Academy of Sciences, New York, pp 1–14Google Scholar
  7. Catterall WA, Perez-Reyes E, Snutch TP, Striennig J (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 57:411–425PubMedGoogle Scholar
  8. Dascal N (1990) Analysis and functional characteristics of dihydropyridine-sensitive and -insensitive calcium channel proteins. Biochem Pharmacol 40:1171–1178PubMedGoogle Scholar
  9. Diversé-Pierluissi M, Goldsmith PK, Dunlap K (1995) Transmitter-mediated inhibition of N-type calcium channels in sensory neurons involves multiple GTP-binding proteins and subunits. Neuron 14:191–200PubMedGoogle Scholar
  10. Dolphin AC (1991) Regulation of calcium channel activity by GTP binding proteins and second messengers. Biochim Biophys Acta 1091:68–80PubMedGoogle Scholar
  11. Ertel SI, Ertel EA, Clozel JP (1997) T-Type calcium channels and pharmacological blockade: potential pathophysiological relevance. Cardiovasc Drugs Ther 11:723–739PubMedGoogle Scholar
  12. Ferrante J, Triggle DJ (1990) Drug- and disease-induced regulation of voltage-dependent calcium channels. Pharmacol Rev 42:29–44PubMedGoogle Scholar
  13. Fisher TE, Bourque CW (1996) Calcium-channel subtypes in the somata and axon terminals of magnocellular neurosecretory cells. Trends Neurosci 19:440–444PubMedGoogle Scholar
  14. Fleckenstein A (1964) Die Bedeutung der energiereichen Phosphate für Kontraktilität und Tonus des Myocards. Verh Dtsch Ges Inn Med 70:81–99PubMedGoogle Scholar
  15. Fleckenstein A (1983) History of calcium antagonists. Circ Res 52(Suppl I):3–16Google Scholar
  16. Fleckenstein A, Kammermeier H, Döring HJ, Freund HJ (1967) Zum Wirkungsmechanismus neuartiger Koronardilatatoren mit gleichzeitig Sauerstoff einsparenden Myocardeffekten, Prenylamin. Irpoveratril Z Kreislaufforsch 56(716–744):839–853Google Scholar
  17. Fleckenstein A, Frey M, Fleckenstein-Grün G (1983) Consequences of uncontrolled calcium entry and its prevention with calcium antagonists. Eur Heart J 4(Suppl H):43–50PubMedGoogle Scholar
  18. Fleckenstein A, Frey M, Fleckenstein-Grün G (1986) Antihypertensive and arterial anticalcinotic effects of calcium antagonists. Am J Cardiol 57:1D–10DPubMedGoogle Scholar
  19. Galizzi JP, Quar J, Fosset M, Van Renterghem C, Lazdunski M (1987) Regulation of calcium channels in aortic muscle cells by protein kinase C activators (diacylglycerol and phorbol esters) and by peptides (vasopressin and bombesin) that stimulate phosphoinositide breakdown. J Biol Chem 262:6947–6950PubMedGoogle Scholar
  20. Hockerman GH, Peterson BZ, Johnson BD, Catterall WA (1997) Molecular determinants of drug binding and action on L-type calcium channels. Annu Rev Pharmacol Toxicol 37:361–396PubMedGoogle Scholar
  21. Hosey MM, Chang FC, O’Callahan CM, Ptasienski J (1989) L-type channels in cardiac and skeletal muscle: purification and phosphorylation. In: Wray DW, Norman RI, Hess P (eds) Calcium channels: structure and function, vol 560, Annals of the New York Academy of Sciences. New York Academy of Sciences, New York, pp 27–38Google Scholar
  22. Ikeda SR (1996) Voltage-dependent modulation of N-type calcium channels by G-protein βγ -subunits. Nature 380:255–258PubMedGoogle Scholar
  23. Kitamura N, Ohta T, Ito S, Nakazato Y (1997) Calcium channel subtypes in porcine adrenal chromaffin cells. Pflügers Arch Eur J Physiol 434:179–187Google Scholar
  24. Kochegarow AA (2003) Pharmacological modulators of voltage-gated calcium channels and their therapeutic application. Cell Calcium 33:145–162Google Scholar
  25. Maggi CA, Tramontana M, Cecconi R, Santicioli P (1990) Neurochemical evidence of N-type calcium channels in transmitter secretion from peripheral nerve endings of sensory nerves in guinea pigs. Neurosci Lett 114:203–206PubMedGoogle Scholar
  26. Massie BM (1997) Mibefradil: a selective T-type calcium antagonist. Am J Cardiol 80A:231–321Google Scholar
  27. Miljanich GP, Ramachandran J (1995) Antagonists of neuronal calcium channels: structure, function and therapeutic implications. Annu Rev Pharmacol Toxicol 35:707–734PubMedGoogle Scholar
  28. Mintz IM, Adams ME, Bean BP (1992) P-Type calcium channels in rat central and peripheral neurons. Neuron 9:85–95PubMedGoogle Scholar
  29. Mitterdorfer J, Wang Z, Sinnegger MJ, Hering S, Striessnig J, Grabner M, Glossmann H (1996) Two amino acid residues in the IIIS5 segment of L-type calcium channels differentially contribute to 1,4-dihydropyridine sensitivity. J Biol Chem 271:30330–30335PubMedGoogle Scholar
  30. Moresco RM, Govoni S, Battaini F, Trivulzio S, Trabucchi M (1990) Omegaconotoxin binding decreases in aged rat brain. Neurobiol Aging 11:433–436PubMedGoogle Scholar
  31. Nakao SI, Ebata H, Hamamoto T, Kagawa Y, Hirata H (1988) Solubilization and reconstitution of voltage-dependent calcium channel from bovine cardiac muscle. Ca2+ influx assay using the fluorescent dye Quin2. Biochim Biophys Acta 944:337–343PubMedGoogle Scholar
  32. Olivera BM, Cruz LJ, de Santos V, LeCheminant GW, Griffin D, Zeikus R, McIntosh JM, Galyean R, Varga J, Gray WR, Rivier J (1987) Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using ω-conotoxin from Conus magus venom. Biochemistry 26:2086–2090PubMedGoogle Scholar
  33. Perez-Reyes E, Cribbs L, Daud A, Jung-Ha L (1998) Molecular characterization of T-type calcium channels. Naunyn-Schmiedeberg’s Arch Pharmacol 358(Suppl 2):R583Google Scholar
  34. Perez-Reyes E (2003) Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev 83:117–161PubMedGoogle Scholar
  35. Perez-Reyes E (2006) Molecular characterization of T-type calcium channels. Cell Calcium 40:89–96PubMedGoogle Scholar
  36. Peterson BZ, Tanada TN, Catterall WA (1996) Molecular determinants of high affinity dihydropyridine binding in L-type calcium channels. J Biol Chem 271:5293–5296PubMedGoogle Scholar
  37. Porzig H (1990) Pharmacological modulation of voltage-dependent calcium channels in intact cells. Rev Physiol Biochem Pharmacol 114:209–262PubMedGoogle Scholar
  38. Rampe D, Triggle DJ (1993) New synthetic ligands for L-type voltage-gated calcium channels. Progr Drug Res 40:191–238Google Scholar
  39. Reuter H, Porzig H, Kokubun S, Prod’Hom B (1988) Calcium channels in the heart. Properties and modulation by dihydropyridine enantiomers. Ann NY Acad Sci 522:16–24PubMedGoogle Scholar
  40. Rosenberg RL, Isaacson JS, Tsien RW (1989) Solubilization, partial purification, and properties of ω-conotoxin receptors associated with voltage-dependent calcium channels. In: Wray DW, Norman RI, Hess P (eds) Calcium channels: structure and function, vol 560, Annals of the New York Academy of Sciences. New York Academy of Sciences, New York, pp 39–52Google Scholar
  41. Schuster A, Lacinová L, Klugbauer N, Ito H, Birnbaumer L, Hofmann F (1996) The IVS6 segment of the L-type calcium channel is critical for the action of dihydropyridines and phenylalkylamines. EMBO J 15:2365–2370PubMedCentralPubMedGoogle Scholar
  42. Sinnegger MJ, Wang Z, Grabner M, Hering S, Striessnig J, Glossmann H, Mitterdorfer J (1997) Nine L-type amino acid residues confer full 1,4-dihydropyridine sensitivity to the neuronal calcium channel α 1A subunit. J Bill Chem 272:27686–27693Google Scholar
  43. Spedding M, Paoletti R (1992) Classification of calcium channels and the sites of action of drugs modifying channel function. Pharmacol Rev 44:363–376PubMedGoogle Scholar
  44. Striessnig J, Grabner M, Mitterdorfer J, Hering S, Sinneger MJ, Glossmann H (1998) Structural basis of drug binding to L Ca2+ channels. Trends Pharmacol Sci 19:108–115PubMedGoogle Scholar
  45. Striessnig J, Hoda JC, Koschak A, Zaghetto F, Müllner C, Sinnegger-Brauns MJ, Wild C, Watschinger K, Trockenbacher A, Pelster G (2004) L-type Ca2+ channels in Ca2+ channelopathies. Biochem Biophys Res Commun 322:1341–1346PubMedGoogle Scholar
  46. Tsien RW, Tsien RY (1990) Calcium channels, stores and oscillations. Annu Rev Cell Biol 6:715–760PubMedGoogle Scholar
  47. Woppmann A, Ramachandran J, Miljanich GP (1994) Calcium channel subtypes in rat brain: biochemical characterization of the high-affinity receptors for ω-conopeptides SNX-230 (synthetic MVIIC), SNX-183 (SVIB), and SNX-111 (MVIIA). Mol Cell Neurosci 5:350–357PubMedGoogle Scholar

In Vitro Methods

  1. Balwierczak JL, Grupp IL, Grupp G, Schwartz A (1986) Effects of bepridil and diltiazem on [3H] nitrendipine binding to canine cardiac sarcolemma. Potentiation of pharmacological effects of nitrendipine by bepridil. J Pharmacol Exp Ther 237:40–48PubMedGoogle Scholar
  2. Bellemann P, Ferry D, Lübbecke F, Glossmann H (1981) [3H]-Nitrendipine, a potent calcium antagonist, binds with high affinity to cardiac membranes. Arzneim Forsch/Drug Res 31:2064–2067Google Scholar
  3. Boles RG, Yamamura HI, Schoemaker H, Roeske WR (1984) Temperature-dependent modulation of [3H]nitrendipine binding by the calcium channel antagonists verapamil and diltiazem in rat brain synaptosomes. J Pharmacol Exp Ther 229:333–339PubMedGoogle Scholar
  4. Bolger GT, Skolnick P (1986) Novel interactions of cations with dihydropyridine calcium antagonist binding sites in brain. Br J Pharmacol 88:857–866PubMedCentralPubMedGoogle Scholar
  5. Bolger GT, Genko P, Klockowski R, Luchowski E, Siegel H, Janis RA, Triggle AM, Triggle DJ (1983) Characterization of binding of the Ca2+ channel antagonist, [3H]nitrendipine, to guinea pig ileal smooth muscle. J Pharmacol Exp Ther 225:291–309PubMedGoogle Scholar
  6. Campiani G, Fiorini I, De Filippis MP, Ciani SM, Garofalo A, Nacci V, Giorgi G, Sega A, Botta M, Chiarini A, Budriesi R, Bruni G, Romeo MR, Manzoni C, Mennini T (1996) Cardiovascular characterization of pyrrolo[2,1-d] [1,5]benzothiazepine derivatives binding selective to the peripheral-type benzodiazepine receptor (PBR): from dual PBR affinity and calcium antagonist activity to novel and selective calcium entry blockers. J Med Chem 39:2922–2938PubMedGoogle Scholar
  7. Cheng YC, Prusoff WH (1973) Relationship between the inhibition constant (K I) and the concentration of inhibitor which causes 50 per cent inhibition (I 50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108PubMedGoogle Scholar
  8. Cohen CJ, Ertel EA, Smith MM, Venam VJ, Adams ME, Leibowitz MD (1992) High affinity block of myocardial L-type calcium channels by the spider toxin ω-agatoxin IIIA: advantages over 1,4-dihydropyridines. Mol Pharmacol 42:947–951PubMedGoogle Scholar
  9. Ehlert FJ, Itoga E, Roeske WR, Yamamura HI (1982a) The interaction of [3H]nitrendipine with receptors for calcium antagonists in the cerebral cortex and heart of rats. Biochem Biophys Res Commun 104:937–943PubMedGoogle Scholar
  10. Ehlert FJ, Roeske WR, Itoga E, Yamamura HI (1982b) The binding of [3H]nitrendipine to receptors for calcium channel antagonists in the heart, cerebral cortex, and ileum of rats. Life Sci 30:2191–2202PubMedGoogle Scholar
  11. Feigenbaum P, Garcia ML, Kaczorowski GJ (1988) Evidence for distinct sites coupled with high affinity ω-conotoxin receptors in rat brain synaptic plasma membrane vesicles. Biochem Biophys Res Commun 154:298–305PubMedGoogle Scholar
  12. Ferry DR, Glossmann H (1982) Identification of putative calcium channels in skeletal muscle microsomes. FEBS Lett 148:331–337PubMedGoogle Scholar
  13. Ferry DR, Goll A, Gadow C, Glossmann H (1984) (−)-3H-desmethoxyverapamil labelling of putative calcium channels in brain: autoradiographic distribution and allosteric coupling to 1,4-dihydropyridine and diltiazem binding sites. Naunyn Schmiedeberg’s Arch Pharmacol 327:183–187Google Scholar
  14. Ferry DR, Goll A, Glossmann H (1987) Photoaffinity labelling of the cardiac calcium channel. Biochem J 243:127–135PubMedCentralPubMedGoogle Scholar
  15. Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149–177Google Scholar
  16. Fleckenstein A, Kammermeier H, Döring HJ, Freund HJ (1967) Zum Wirkungsmechanismus neuartiger Koronardilatatoren mit gleichzeitig Sauerstoff einsparenden Myocardeffekten, Prenylamin. Irpoveratril Z Kreislaufforsch 56(716–744):839–853Google Scholar
  17. Glossmann H, Ferry DR (1985) Assay for calcium channels. Meth Enzymol 109:513–550PubMedGoogle Scholar
  18. Glossmann H, Linn T, Rombusch M, Ferry DR (1983) Temperature-dependent regulation of d-cis-[3H]diltiazem binding to Ca2+ channels by 1,4-dihydropyridine channel agonists and antagonists. FEBS Lett 160:226–232PubMedGoogle Scholar
  19. Glossmann H, Ferry DR, Goll A, Striessnig J, Schober M (1985a) Calcium channels: basic properties as revealed by radioligand binding studies. J Cardiovasc Pharmacol 7(Suppl 6):S20–S30PubMedGoogle Scholar
  20. Glossmann H, Ferry DR, Goll A, Striessnig J, Zernig G (1985b) Calcium channels and calcium channel drugs: recent biochemical and biophysical findings. Arzneim Forsch/Drug Res 35:1917–1935Google Scholar
  21. Glossmann H, Ferry DR, Striessnig J, Goll A, Moosburger K (1987) Resolving the structure of the Ca2+ channel by photoaffinity labelling. Trends Pharmacol Sci 8:95–100Google Scholar
  22. Goll A, Ferry DR, Striessnig J, Schober M, Glossmann H (1984) (−)-[3H]Desmethoxyverapamil, a novel Ca2+ channel probe. FEBS Lett 176:371–377PubMedGoogle Scholar
  23. Gould RJ, Murphy KMM, Snyder SH (1982) [3H]Nitrendipine-labeled calcium channels discriminate inorganic calcium agonists and antagonists. Proc Natl Acad Sci U S A 79:3656–3660PubMedCentralPubMedGoogle Scholar
  24. Gould RJ, Murphy KMM, Snyder SH (1983) Tissue heterogeneity of calcium channel antagonist binding sites labeled by [3H]nitrendipine. Mol Pharmacol 25:235–241Google Scholar
  25. Grassegger A, Striessnig J, Weiler M, Knaus HG, Glossmann H (1989) [3H]HOE 166 defines a novel calcium antagonist drug receptor – distinct from the 1,4-dihydropyridine binding domain. Naunyn Schmiedeberg’s Arch Pharmacol 340:752–759Google Scholar
  26. He M, Bodi I, Mikala G, Schwartz A (1997) Motif III S5 of L-type channels is involved in the dihydropyridine binding site. J Biol Chem 272:2629–2633PubMedGoogle Scholar
  27. Ichida S, Wada T, Nakazaki S, Matsuda N, Kishino H, Akimoto T (1993) Specific bindings of [3H](+)PN200–110 and [125]omega-conotoxin to crude membranes from differentiated NG 108–15 cells. Neurochem Res 18:633–638PubMedGoogle Scholar
  28. Ikeda S, Amano Y, Adachi-Akahane S, Nagao T (1994) Binding of [3H](+)PN200–110 to aortic membranes from normotensive and spontaneously hypertensive rats. Eur J Pharmacol 264:223–226PubMedGoogle Scholar
  29. Janis RA, Sarmianto JG, Maurer SC, Bolger GT, Triggle DJ (1984) Characteristics of the binding of [3H]nitrendipine to rabbit ventricular membranes: modification by other Ca2+ channel antagonists and by the Ca2+ channel agonist Bay K 8644. J Pharmacol Exp Ther 231:8–15PubMedGoogle Scholar
  30. Kalasz H, Watanabe T, Yabana H, Itagaki K, Naito K, Nakayama H, Schwartz A, Vaghy PL (1993) Identification of 1,4-dihydropyridine binding domains within the primary structure of the α 1 subunit of the skeletal muscle L-type calcium channel. FEBS Lett 331:177–181PubMedGoogle Scholar
  31. Knaus HG, Moshammer T, Kang HC, Haugland RP, Glossmann H (1992) A unique fluorescent phenylalkylamine probe for L-type Ca2+ channels. J Biol Chem 267:2179–2189PubMedGoogle Scholar
  32. Lee HR, Roeske WR, Yamamura HI (1984) High affinity specific [3H](+)PN 200–110 binding to dihydropyridine receptors associated with calcium channels in rat cerebral cortex and heart. Life Sci 35:721–732PubMedGoogle Scholar
  33. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein Measurement with the Folin Phenol Reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  34. Matthes J, Huber I, Haaf O, Antepohl W, Striessnig J, Herzig S (2000) Pharmacodynamic interaction between mibefradil and other calcium channel blockers. Naunyn-Schmiedebergs Arch Pharmacol 361:578–583PubMedGoogle Scholar
  35. Miwa K, Miyagi Y, Araie E, Sasayama S (1992) Effects of diltiazem and verapamil on (+)-PN 200–110 binding kinetics in dog cardiac membranes. Eur J Pharmacol 213:127–132Google Scholar
  36. Marangos PJ, Patel J, Miller C, Martino AM (1982) Specific calcium antagonist binding sites in brain. Life Sci 31:1575–1585PubMedGoogle Scholar
  37. Naito K, McKenna E, Schwartz A, Vaghy PI (1989) Photoaffinity labeling of the purified skeletal muscle calcium antagonist receptor by a novel benzodiazepine, [3H]azidobutyryl diltiazem. J Biol Chem 264:21211–21214PubMedGoogle Scholar
  38. Natale NR, Rogers ME, Staples R, Triggle DJ, Rutledge A (1999) Lipophilic 4-isoxazolyl-1,4-dihydropyridines: synthesis and structure-activity relationships. J Med Chem 42:3087–3093PubMedGoogle Scholar
  39. Nokin P, Clinet M, Beaufort P, Meysman L, Laruel R, Chatelain P (1990) SR 33557, a novel calcium entry blocker. II Interactions with 1,4-dihydropyridine, phenylalkylamine, and benzodiazepine binding sites in rat heart sarcolemmal membranes. J Pharmacol Exp Ther 255:600–607PubMedGoogle Scholar
  40. Peri R, Padmanabhan S, Rutledge A, Singh S, Triggle DJ (2000) Permanently charged chiral 1,4-dihydropyridines: molecular probes of L-type calcium channels. Synthesis and pharmacological characterization of methyl-(ω-trimethylalkylammonium 1,4-dihydro-2,6-dimethyl-4-(3-nitro-phenyl)-3,5-pyridinecarboxylate iodide, calcium channel antagonists. J Med Chem 43:2906–2914PubMedGoogle Scholar
  41. Reynolds IJ, Snowman AM, Snyder SH (1986) (−)-[3H]Desmethoxyverapamil labels multiple calcium channel modulator receptors in brain and skeletal muscle membranes: differentiation by temperature and dihydropyridines. J Pharmacol Exp Ther 237:731–738PubMedGoogle Scholar
  42. Ruth P, Flockerzi V, von Nettelblatt V, Oeken J, Hoffmann F (1985) Characterization of binding sites for nimodipine and (−)-desmethoxyverapamil in bovine sarcolemma. Eur J Biochem 150:313–322PubMedGoogle Scholar
  43. Rutledge A, Triggle DJ (1995) The binding interactions of Ro 40–5967 at the L-type Ca2+ channel in cardiac tissue. Eur J Pharmacol 280:155–158PubMedGoogle Scholar
  44. Salter F, Grover AK (1987) Characterization and solubilization of the nitrendipine binding protein from canine small intestinal circular smooth muscle. Cell Calcium 8:145–166PubMedGoogle Scholar
  45. Schoemaker H, Langer SZ (1985) [3H]diltiazem binding to calcium channel antagonists recognition sites in rat cerebral cortex. Eur J Pharmacol 111:273–277PubMedGoogle Scholar
  46. Shimasue K, Urushidani T, Hagiwara M, Nagao T (1996) Effects of anandamide and arachidonic acid on specific binding of (+)-PN200–110 and (?)-desmethoxyverapamil to L-type Ca2+ channel. Eur J Pharmacol 296:347–350PubMedGoogle Scholar
  47. Striessnig J, Murphy BJ, Catterall WA (1991) Dihydropyridine receptor of L-type Ca2+ channels: identification of binding domains for [3H](+)-PN200–110 and [3H]azidopine within the α1 subunit. Proc Natl Acad Sci U S A 88:10769–10773PubMedCentralPubMedGoogle Scholar
  48. Vaghy PI, Striessnig J, Miwa K, Knaus HG, Itagati K, McKenna E, Glossmann H, Schwartz A (1987) Identification of a novel 1,4-dihydropyridine- and phenylalkylamine-binding polypeptide in calcium channel preparations. J Biol Chem 262:14337–14342PubMedGoogle Scholar
  49. Wagner JA, Snowman AM, Biswas A, Olivera BM, Snyder SH (1988) ω-Conotoxin GVIA binding to a high-affinity receptor in brain: characterization, calcium sensitivity, and solubilization. J Neurosci 8:3354–3359PubMedGoogle Scholar
  50. Watanabe T, Kalasz H, Yabana H, Kuniyasu A, Mershon J, Itagaki K, Vaghy PL, Naito K, Nakayama H, Schwartz A (1993) Azidobutyryl clentiazem, a new photoactivable diltiazem analog, labels benzothiazepine binding sites in the α 1 subunit of the skeletal muscle calcium channel. FEBS Lett 334:261–264PubMedGoogle Scholar
  51. Weiland GA, Oswald RE (1985) The mechanism of binding of dihydropyridine calcium channel blockers to rat brain membranes. J Biol Chem 260:8456–8464PubMedGoogle Scholar
  52. Yaney GC, Stafford A, Henstenberg JD, Sharp GWG, Weiland GA (1991) Binding of the dihydropyridine calcium channel blocker (+)-[3H]isopropyl-4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxy-carbonyl-2,6-dimethyl-3- pyridinecarboxylate (PN200–110) to RINm5F membranes and cells. Characterization and functional significance. J Pharmacol Exp Ther 258:652–662PubMedGoogle Scholar

Calcium Antagonism in Isolated Organs

  1. Grupp IL, Grupp G (1984) Isolated heart preparations perfused or superfused with balanced salt solutions. In: Schwartz A (ed) Methods in pharmacology, vol 5. Myocardial biology. Plenum, New York/London, pp 111–128Google Scholar
  2. Kohlhardt M, Fleckenstein A (1977) Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. Naunyn Schmiedeberg’s Arch Pharmacol 298:267–272Google Scholar
  3. Linz W, Schölkens BA, Kaiser J, Just M, Bei-Yin Q, Albus U, Petry P (1989) Cardiac arrhythmias are ameliorated by local inhibition of angiotensin formation and bradykinin degradation with the converting-enzyme inhibitor ramipril. Cardiovasc Drugs Ther 3:873–882PubMedGoogle Scholar
  4. Striessnig J, Meusburger E, Grabner M, Knaus HG, Glossmann H, Kaiser J, Schölkens B, Becker R, Linz W, Henning R (1988) Evidence for a distinct Ca2+ antagonist receptor for the novel benzothiazinone compound Hoe 166. Naunyn-Schmiedeberg’s Arch Pharmacol 337:331–340Google Scholar

Calcium Antagonism in the Isolated Guinea Pig Atrium

  1. Church J, Zsotér TT (1980) Calcium antagonistic drugs. Mechanism of action. Can J Physiol Pharmacol 58:254–264PubMedGoogle Scholar
  2. Grupp IL, Grupp G (1984) Isolated heart preparations perfused or superfused with balanced salt solutions. In: Schwartz A (ed) Methods in pharmacology, vol 5. Myocardial biology. Plenum, New York/London, pp 111–128Google Scholar
  3. Leboeuf J, Baissat J, Massingham R (1992) Protective effect of bepridil and against veratrine-induced contracture in rat atria. Eur J Pharmacol 216:183–189PubMedGoogle Scholar
  4. Lindner E, Ruppert D (1982) Effects of calcium antagonists on coronary spasm and pulmonary artery contraction in comparison to their antagonistic action against K-strophanthin in isolated guinea-pig atria. Pharmacology 24:294–302Google Scholar
  5. Rajagopalan R, Ghate AV, Subbarayan P, Linz W, Schoelkens BA (1993) Cardiotonic activity of the water soluble forskoline derivative 8,13-epoxy-6β-(piperidinoacetoxy)-1α,7β,9α-trihydroxy-labd-14-en-11-one. Arzneim Forsch/Drug Res 43(I):313–319Google Scholar
  6. Salako LA, Vaugham Williams EM, Wittig JH (1976) Investigations to characterize a new anti-arrhythmic drug, ORG 6001, including a simple test for calcium antagonism. Br J Pharmacol 57:251–262PubMedCentralPubMedGoogle Scholar

Calcium Antagonism in the Isolated Rabbit Aorta

  1. Hof RP, Vuorela HJ (1983) Assessing calcium antagonism on vascular smooth muscle: comparison of three methods. J Pharmacol Methods 9:41–52PubMedGoogle Scholar
  2. Matsuo K, Morita S, Uchida MK, Sakai K (1989) Simple and specific assessment of Ca-entry-blocking activities of drugs by measurement of Ca reversal. J Pharmacol Methods 22:265–275PubMedGoogle Scholar
  3. Micheli D, Collodel A, Semerano C, Gaviraghi G, Carpi C (1990) Lacidipine: a calcium antagonist with potent and long-lasting antihypertensive effects in animal studies. J Cardiovasc Pharmacol 15:666–675PubMedGoogle Scholar
  4. Rüegg UT, Doyle VM, Zuber JF, Hof RP (1985) A smooth muscle cell line suitable for the study of voltage sensitive calcium channels. Biochem Biophys Res Commun 130:447–453PubMedGoogle Scholar
  5. Robinson CP, Sastry BVR (1976) The influence of mecamylamine on contraction induced by different agonists and the role of calcium ions in the isolated rabbit aorta. J Pharmacol Exp Ther 197:57–65PubMedGoogle Scholar
  6. Striessnig J, Meusburger E, Grabner M, Knaus HG, Glossmann H, Kaiser J, Schölkens B, Becker R, Linz W, Henning R (1988) Evidence for a distinct Ca2+ antagonist receptor for the novel benzothiazinone compound Hoe 166. Naunyn-Schmiedeberg’s Arch Pharmacol 337:331–340Google Scholar
  7. Towart R (1982) Effects of nitrendipine (Bay e 5009), nifedipine, verapamil, phentolamine, papaverine, and minoxidil on contractions of isolated rabbit aortic smooth muscle. J Cardiovasc Pharmacol 4:895–902PubMedGoogle Scholar
  8. Turner RA (1965) Cardiotonic agents; The aortic strip of the rabbit. In: Turner RA (ed) Screening methods in pharmacology. Academic, New York/London, pp 203–209Google Scholar

Calcium Antagonism in the Isolated Guinea Pig Pulmonary Artery

  1. Green AF, Boura ALA (1964) Sympathetic nerve blockade. In: Laurence DR, Bacharach AL (eds) Evaluation of drug activities: pharmacometrics. Academic, London/New York, pp 370–430Google Scholar
  2. Lindner E, Ruppert D (1982) Effects of Ca2+ antagonists on coronary spasm and pulmonary artery contraction in comparison to their antagonistic action against k-strophanthin in isolated guinea-pig atria. Pharmacology 24:294–302Google Scholar
  3. Striessnig J, Meusburger E, Grabner M, Knaus HG, Glossmann H, Kaiser J, Schölkens B, Becker R, Linz W, Henning R (1988) Evidence for a distinct Ca2+ antagonist receptor for the novel benzothiazinone compound Hoe 166. Naunyn-Schmiedeberg’s Arch Pharmacol 337:331–340Google Scholar

In Vivo Methods

  1. Clapham JC (1988) A method for in vivo assessment of calcium slow channel blocking drugs. J Cardiovasc Pharmacol 11:56–60PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Michael Gralinski
    • 1
  • Liomar A. A. Neves
    • 1
  • Olga Tiniakova
    • 1
  1. 1.CorDynamics, Inc.ChicagoUSA

Personalised recommendations