Summary
Effects of pentobarbital on acetylcholine (ACh) release, force of contraction and nervous conduction were studied in isolated heart preparations and in cervical vagus nerves, respectively. 4-Aminopyridine and tetracaine were used as pharmacological tools to eludicate the mode of action of pentobarbital.
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1.
4-Aminopyridine (10−4 M) markedly increased the overflow of ACh from the isolated chicken heart evoked by electrical stimulation (1–50 Hz, 1 ms, 40 V) of the cervical vagus nerves. This effect of 4-aminopyridine was highest at low frequencies of stimulation (+ 226% at 1 Hz) and declined with increasing frequencies to reach a minimum augmentation of 22% at 30 Hz.
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2.
Pentobarbital and tetracaine dose-dependently decreased the evoked overflow of ACh from the isolated chicken heart. Half-maximal inhibition was observed at concentrations (IC50) of 1.4×10−4 M and 4×10−6 M, respectively. Much higher concentrations of pentobarbital were required to inhibit the conduction in vagal B-fibres (IC50=3×10−3 M) whereas the IC50 values of tetracaine for both inhibitory effects were nearly identical.
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3.
4-Aminopyridine (10−4 M) antagonized the inhibitory effect of PB on the evoked overflow of ACh and shifted the concentration-response curve to the right. The 4-aminopyridine/pentobarbital antagonism was equally pronounced whether the release of ACh was evoked by vagal stimulation (preganglionic) or by field stimulation (pre- and postganglionic).
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4.
The negative inotropic effect of vagal stimulation in isolated atria of cats and chickens was weakened by pentobarbital (1–5×10−4 M) and enhanced by 4-aminopyridine (10−4 M). Again, 4-aminopyridine (10−4 M) antagonized the effect of pentobarbital.
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5.
In contrast to the effects of pentobarbital, the inhibition of ACh overflow produced by tetracaine was not antagonized by 4-aminopyridine.
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6.
The results strongly support the previous suggestion (Lindmar et al., 1979) that the inhibition by pentobarbital of the evoked overflow of ACh from the postganglionic parasympathetic neurones of the heart is due to a reduction of the Ca2+ inward current into the nerve terminals.
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This work was supported by the Deutsche Forschungsgemeinschaft
The results are part of the Ph.D. thesis of W.W.
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Weide, W., Löffelholz, K. 4-Aminopyridine antagonizes the inhibitory effect of pentobarbital on acetylcholine release in the heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 312, 7–13 (1980). https://doi.org/10.1007/BF00502566
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DOI: https://doi.org/10.1007/BF00502566