Nicotine-induced release of noradrenaline and neuropeptide Y in guinea-pig heart: role of calcium channels and protein kinase C.
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)
Haass
M
M
Department of Cardiology, University of Heidelberg, Federal Republic of Germany.
Richardt
G
G
Brenn
T
T
Schömig
E
E
Schömig
A
A
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D015736:Felodipine / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*
D015220:Calcium Channels; D009478:Neuropeptide Y; D009538:Nicotine; D011493:Protein Kinase C; D015736:Felodipine; D009638:Norepinephrine