Nicotine-induced release of noradrenaline and neuropeptide Y in guinea-pig heart: role of calcium channels and protein kinase C

M Haass, G Richardt, T Brenn, E Schömig, A Schömig

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The role of calcium, calcium influx through calcium channels, and activation of protein kinase C for the nicotine-induced release of noradrenaline and of the sympathetic co-transmitter neuropeptide Y (NPY) was investigated in the guinea-pig isolated perfused heart. In the coronary venous overflow noradrenaline and NPY were determined by high-pressure liquid chromatography and radioimmunoassay, respectively. In the presence of extracellular calcium (1.85 mmol/l) nicotine (1-100 mumol/l) evoked a concentration-dependent overflow of both transmitters with a molar ratio of approximately 1500 (noradrenaline):1 (NPY). The nicotine-induced (100 mumol/l) overflow of noradrenaline and NPY was in a linear manner related (r = 0.79 and 0.90, respectively; p less than 0.05) to the extracellular calcium concentration (0-1.85 mmol/l), and it was prevented by calcium-free perfusion. The L-type calcium channel blocker felodipine (100 nmol/l) did not affect the nicotine-induced (100 mumol/l) transmitter overflow. On the other hand, the neuronal (N-type) calcium channel blockers omega-conotoxin (100 nmol/l) and cadmium chloride (50 mumol/l) reduced the nicotine-induced (100 mumol/l) transmitter overflow to 20% of the control value, suggesting a role of N-type calcium channels in mediating the calcium influx for the nicotine-induced transmitter release. The nicotine-induced (30 mumol/l) overflow of both transmitters was two- to three-fold increased by activation of protein kinase C (phorbol 12-myristate 13-acetate; 100 nmol/l). The transmitter overflow was unaffected by 4 alpha-phorbol 12,13-didecanoate (100 nmol/l), a phorbol ester which does not stimulate protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish
Pages (from-to)527-31
Number of pages5
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume344
Issue number5
Publication statusPublished - Nov 1991

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Calcium Channels
  • Chromatography, High Pressure Liquid
  • Felodipine
  • Guinea Pigs
  • Heart
  • Myocardium
  • Neuropeptide Y
  • Nicotine
  • Norepinephrine
  • Protein Kinase C

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