An Endogenous Purified Peptide Modulates Ca2+ Channels in Neurons and Cardiac Myocytes

  • I. Hanbauer
  • E. Sanna
  • G. Callewaert
  • M. Morad
Conference paper
Part of the Bayer AG Centenary Symposium book series (BAYER)

Abstract

Transport of Ca2+ through membrane channels plays an important role in excitation-contraction coupling of cardiac and smooth muscle, in neurosecretion, and in neuronal signaling. The discovery that dihydropyridines can regulate voltage-activated Ca2+ channels (Fleckenstein et al. 1972) set the stage for studies on the structure and function of these channels and provided a biochemical probe useful in the search for possible endogenous modulators (EMs). Studies on the existence of endogenous Ca2+ -channel modulators were triggered by various reports providing electrophysiological and pharmacological evidence for the involvement of organic Ca2+ -channel antagonists in Ca2+ -channel regulation (Fleckenstein 1977; Janis and Diamond 1981; Tsien 1984). Supporting the idea of the possible existence of EMs were reports showing that sympathetic denervation of the heart up-regulated the dihydropyridine binding sites in this tissue (Skattebol1986) and that up-regulation of 3H-nitrendipine binding sites occurred in mouse brain after chronic treatment with morphine (Ramkumar and El-Fakahany1984). Janis et al. (1988) have reported that a number of endogenous substances alter Ca2+ -channel activity by either inhibiting 3H-dihydropyridine binding or modifying potential-dependent Ca2+ currents. For example, dynorphine A inhibited Ca2+ -channel activity, while calcitoninlike peptides enhanced the Ca2+ channel without altering 3H-dihydropyridine binding (Nohmi et al. 1985; Tsunoo et al. 1986; MacDonald and Merz 1987).

Keywords

Dopamine Morphine Serotonin Methylenechloride Catecholamine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Borsotto M, Norman RI, Fosset M, Lazdunski M (1984) Solubilization of the nitrendipine receptor from skeletal muscle transverse tubule membranes. Interactions with specific inhibitors of the voltage-dependent Ca2+ channel. Eur J Biochem 142:449–455PubMedCrossRefGoogle Scholar
  2. Carboni E, Wojcik WJ, Costa E (1985) Dihydropyridine changes the uptake of Ca2+ induced by depolarization in primary cultures of cerebellar granule cells. Neuropharmacology 24:1123–1126PubMedCrossRefGoogle Scholar
  3. Curtis BM, CatterallWA (1983) Solubilization of the calcium antagonist receptor from rat brain. J Biol Chern 258:7280–7283Google Scholar
  4. Fleckenstein A, Tritthart H, Doring H-J, Byon YK (1972) Bay a 1040 — ein hochaktiver Ca2+antagonistischer Inhibitor der elektro-mechanischen Koppelungsprozesse im Warmblüter-Myokard. Arnzeimittelforsch 22:22–33Google Scholar
  5. Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149–166CrossRefGoogle Scholar
  6. Glossmann H, Ferry DR (1983) Solubilization and partial purification of putative calcium channels labelled with [3H]-nitrendipine. Naunyn Schmiedeberg’s Arch Pharmacol 323:279–291CrossRefGoogle Scholar
  7. Hanbauer I, Sanna E (1986) Endogenous modulator for nitrendipine binding sites. Clinical Neuropharmacology 9 Suppl 4:220–222PubMedGoogle Scholar
  8. Hanbauer I, Sanna E (1988) Presence in brain of an endogenous ligand for nitrendipine binding sites that modulates Ca2+ channel activity. Ann NY Acad Sci 522:96–105PubMedCrossRefGoogle Scholar
  9. MacDonald RL, Werz MA (1987) Dynorphin A decreases voltage-dependent calcium conductance of mouse dorsal root ganglion neurones. J Physiol (Lond) 377:237–249Google Scholar
  10. Mir AK, Spedding M (1986) Proc Brit Pharmacol Soc 88:381PGoogle Scholar
  11. Mitra R, Morad M (1986) Two types of calcium channels in guinea pig ventricular myocytes. Proc Natl Acad Sci USA 83:5340–5344PubMedCrossRefGoogle Scholar
  12. Nohmi M, Shinnick-Gallagher P, Green PW, Gallagher JP, Cooper CW (1985) Soc Neurosci Abstr 11:708Google Scholar
  13. Ramkumar V, El-Fakahany EE (1984) Increase in [3H]-nitrendipine binding site in the brain in morphine-tolerant mice. Eur J Pharmacol 102:371–2PubMedCrossRefGoogle Scholar
  14. Rampe D, Triggle DJ (1987) Benzodiazepine interactions at neuronal and smooth muscle Ca2+ channels. Eur J Pharmacol 134:189–197PubMedCrossRefGoogle Scholar
  15. Sanna E, Hanbauer I (1987) Isolation from rat brain tissue of an inhibiting activity for dihydropyridine binding sites and voltage-dependent Ca2+ uptake. Neuropharmacology 26:1811–1814PubMedCrossRefGoogle Scholar
  16. Sanna E, Wright AG Jr, Daly JW, Hanbauer I (1988) Dihydropyridine-sensitive Ca2+ channels in rat brain: modulation by an endogenous ligand. In: Fidia Research Series, Symposia in Neuroscience VI Liviana Press, Padova, Italy, pp 123–132Google Scholar
  17. Skattebol A, Triggle DJ (1986) 6-Hydroxydopamine treatment increases B-adrenoceptors and Ca2+ channels in rat heart. Eur J Pharmacol 127:287–289PubMedCrossRefGoogle Scholar
  18. Taft WC, Delorenzo RJ (1984) Micromolar-affinity benzodiazepine receptors regulate voltagesensitive calcium channels in nerve terminal preparations. Proc Natl Acad Sci USA 81:3118–3122PubMedCrossRefGoogle Scholar
  19. Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S (1987) Primary structure of the receptor for Ca2+ channel blockers from skeletal muscle. Nature (Lond) 328:313–318CrossRefGoogle Scholar
  20. Tsien RW (1983) Calcium channels in excitable cell membranes. Annu Rev Physiol 45:341–358PubMedCrossRefGoogle Scholar
  21. Tsunoo A, Yoshii M, Narahashi T (1986) Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG 108–15 cells. Proc Natl Acad Sci USA 83:9832–9836PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • I. Hanbauer
    • 1
  • E. Sanna
    • 1
  • G. Callewaert
    • 2
  • M. Morad
    • 2
  1. 1.Hypertension Endocrine Branch, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Department of PhysiologyUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations