Abstract
The aim of the present study was to explore possible prejunctional effects mediated by impulse activity of sympathetic terminals on evoked acetylcholine release in an organ innervated by the autonomic ground plexus. Rabbit atria were isolated with the extrinsic right vagus and sympathetic nerves intact and perfused with Tyrode solution. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline and fractionation of the radioactivity on cation exchange columns. The overflow of endogenous noradrenaline was measured by HPLC and electrochemical detection.
The vagus nerve was stimulated at 2 Hz for 3 min four times at intervals of 10 min. During the second stimulation the postganglionic sympathetic nerves were stimulated (2 Hz, 3 min) in such a way that the impulses preceded the vagus stimuli by a fixed time interval which was varied in different experiments (0, 7, 19, 50, 132, and 350 ms). Evoked acetylcholine release was significantly enhanced when the vagus was excited 7, 19 and 50 ms after the sympathetic nerves but it was unaltered at the 132 or 350 ms intervals, and when both nerves were stimulated simultaneously. Noradrenaline release was similar (about 6 ng per stimulation period) in all experimental groups. When sympathetic nerve stimulation had little effect in releasing noradrenaline (<2.0 ng per stimulation period), facilitation of acetylcholine release at the 19 ms pulse interval was absent. The resting outflow of acetylcholine was unaffected by sympathetic nerve stimulation.
The experiments show a facilitation of evoked acetylcholine release by sympathetic activity. As revealed by the pulse-to-pulse method this effect is confined to a relatively brief interval immediately following the excitation of the noradrenergic terminal, and is unlikely to be mimicked by exogenous drug application.
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References
Beani L, Bianchi C, Crema A (1969) The effect of catecholamines and sympathetic stimulation on the release of acetylcholine from the guinea-pig colon. Br J Pharmacol 36:1–17
Bognar IT, Beinhauer B, Kann P, Fuder H (1990) Different muscarinic receptors mediate autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat isolated perfused heart. Naunyn-Schmiedeberg's Arch Pharmacol 341:279–287
Dunnett CW (1964) New tables for multiple comparisons with a control. Biometrics 20:482–491
Ehinger B, Falck B, Sporrong B (1970) Possible axo-axonal synapses between peripheral adrenergic and cholinergic nerve terminals. Z Zellforsch 107:508–521
Fozard JR, Muscholl E (1971) A useful muscarinic parameter and the differential recording of atrial and ventricular tension in the perfused rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 270:319–325
Fuder H, Muscholl E (1994) Heteroreceptor-mediated modulation of noradrenaline and acetylcholine release from peripheral nerves. Rev Physiol Biochem Pharmacol 126:265–412
Habermeier-Muth A, Muscholl E (1988) Short- and long-latency muscarinic inhibition of noradrenaline release from rabbit atria induced by vagal stimulation. J Physiol (Lond) 401:277–293
Habermeier-Muth A, Muscholl E (1995) Co-transmitter mediated facilitation by sympathetic nerve stimulation of evoked acetylcholine release from the rabbit perfused atria preparation. Naunyn-Schmiedeberg's Arch Pharmacol 351:164–172
Habermeier-Muth A, Altes U, Forsyth KM, Muscholl E (1990) A presynaptic excitatory M1 muscarine receptor at postganglionic cardiac noradrenergic nerve fibres that is activated by endogenous acetylcholine. Naunyn-Schmiedeberg's Arch Pharmacol 342:483–489
Hillarp N-A (1959) The construction and functional organization of the autonomic innervation apparatus. Acta Physiol Scand 46: [Suppl 157] 1–38
Kilbinger H, Wessler I (1979) Increase by α-adrenolytic drugs of acetylcholine release evoked by field stimulation of the guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 309:255–257
Löffelholz K, Muscholl E (1970) Inhibition by parasympathetic nerve stimulation of the release of the adrenergic transmitter. Naunyn-Schmiedeberg's Arch Pharmacol 267:181–184
Loiacono RE, Story DF (1986) Effect of α-adrenoceptor agonists and antagonists on cholinergic transmission in guinea-pig isolated atria. Naunyn-Schmiedeberg's Arch Pharmacol 334:40–47
Manabe N, Foldes FF, Töröcsik A, Nagashima H, Goldiner PL, Vizi ES (1991) Presynaptic interaction between vagal and sympathetic innervation in the heart: modulation of acetylcholine and noradrenaline release. J Auton Nerv Syst 32:233–242
Manber L, Gershon MD (1979) A reciprocal adrenergic-cholinergic axoaxonic synapse in the mammalian gut. Am J Physiol 236:E738-E745
Marcoli M, Lecchini S, De Ponti F, D'Angelo L, Crema A, Frigo GM (1985) Subsensitivity of enteric cholinergic neurones to α2-adrenoceptor agonists after chronic sympathetic denervation. Naunyn-Schmiedeberg's Arch Pharmacol 329:271–277
Muscholl E (1980) Peripheral muscarinic control of norepinephrine release in the cardiovascular system. Am J Physiol 239:H713-H720
Muscholl E, Habermeier-Muth A (1991) Pulse-to-pulse dependent effect of sympathetic cardiac nerve stimulation on acetylcholine overflow evoked by vagus nerve stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 343:[Suppl] R88
Muscholl E, Muth A (1982) The effect of physostigmine on the vagally induced muscarinic inhibition of noradrenaline release from the isolated rabbit atria. Naunyn-Schmiedeberg's Arch Pharmacol 320:160–169
Paton WDM, Vizi ES (1969) The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol 35:10–28
Racké K, Muscholl E (1986) Release of endogenous 3,4-dihydroxy-phenylethylamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland. Effects of electrical stimulation and of inhibition of monoamine oxidase and reuptake. J Neurochem 46:745–752
Rand MJ, Story DF, Allen GS, Glover AB, McCulloch MW (1973) Pulse-to-pulse modulation of noradrenaline release through a prejunctional α-receptor autoinhibitory mechanism. In: Usdin E, Snyder SH (eds) Frontiers in catecholamine research. Pergamon Press Oxford, pp 579–581
Sachs L (1984) Angewandte Statistik, 6th edn. Springer, Berlin Heidelberg New York Tokyo
Thoenen H, Tranzer JP (1968) Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn-Schmiedeberg's Arch Pharmacol 261:271–288
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Habermeier-Muth, A., Muscholl, E. Impulse interval-dependent effect of sympathetic nerve stimulation on evoked acetylcholine release from the rabbit perfused atria preparation. Naunyn-Schmiedeberg's Arch Pharmacol 351, 156–163 (1995). https://doi.org/10.1007/BF00169329
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DOI: https://doi.org/10.1007/BF00169329