Nicotine receptors do not modulate the 3H-Noradrenaline release from the isolated rat heart evoked by sympathetic nerve stimulation |
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Authors: | H Fuder R Siebenborn E Muscholl |
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Institution: | (1) Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, D-6500 Mainz, Federal Republic of Germany |
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Abstract: | Summary Isolated rat hearts with the right sympathetic nerves attached were perfused at a constant flow rate of 7 ml/min with Tyrode's solution. (-)-3H-Noradrenaline (final concentration 10–13.9 nM) was infused for 10 min to label the noradrenaline stores. After wash-out the sympathetic nerves were stimulated electrically (3 Hz, 180 impulses, 1 ms, 20–30 mA) three times (S1–S3) at intervals of 15 min. 3H-Noradrenaline and its metabolites were determined by liquid scintillation counting according to Graefe et al. (1973).Both, nicotine 50 M and p-aminophenethyltrimethylammonium (PAPETA) 30 M, enhanced the 3H-noradrenaline overflow in the absence of nerve stimulation. The effect of PAPETA was biphasic and was still observed in the presence of N-methylatropine 0.1 M. Hexamethonium 10 M abolished the first phase only, but cocaine 10 M antagonized both phases.The decline of the stimulation-evoked overflow of 3H-noradrenaline from the first to the third stimulation period was similar in the absence and in the presence of cocaine 10 M starting before S1 and perfused throughout. Cocaine 10 M added before S2, however, enhanced the evoked overflow by 77%.PAPETA 30 M increased the stimulation-evoked overflow by 67% in the absence, and by 73% of the respective control in the presence, of hexamethonium 10 M. PAPETA 30 M failed to enhance the evoked overflow in the presence of cocaine. Hexamethonium (added before S2) did not modify the effectiveness of nerve stimulation.Nicotine, neither when perfused from 6 min before S2, nor when added to the perfusion fluid simultaneously with the onset of nerve stimulation, caused changes in the 3H-noradrenaline output upon S2.Upon stimulation a rather discrete increase in 3H-DOPEG overflow was observed. This increase was abolished by cocaine and/or PAPETA.It is concluded that nicotine and PAPETA stimulate the output of 3H-noradrenaline from the rat heart sympathetic nerves by activation of nicotine receptors. However, the amount of transmitter released is small. Neither drug appeared to modulate the output of 3H-noradrenaline upon electrical nerve stimulation via nicotine receptors.PAPETA, like cocaine, appears to block the reuptake of released transmittsrs thereby enhancing the 3H-noradrenaline overflow and reducing the overflow of 3H-DOPEG (formed intraneuronally from recaptured noradrenaline after nerve stimulation).Abbreviations used DOMA
3,4-dihydroxymandelic acid
- DOPEG
3,4-dihydroxyphenylglycol
- MOPEG
3-methoxy-4-hydroxy-phenylglycol
- NA
noradrenaline
- NMN
normetanephrine
- OMDA
O-methylated deaminated metabolites (sum of MOPEG and VMA)
- PAPETA
p-aminophenethyltrimethylammonium
- VMA
3-methoxy-4-hydroxymandelic acid |
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Keywords: | 3H-Noradrenaline and its metabolites Rat heart Sympathetic nerve stimulation Nicotine receptors |
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