Summary
Rat isolated hearts with the sympathetic nerves attached were perfused with (-)-3H-noradrenaline in order to label the storage vesicles of the adrenergic nerves. Release was induced either by electrical stimulation of the nerves (3 Hz, 1 min) or by perfusion with high K+ solution (54 mM). The overflow of 3H-noradrenaline and its metabolites was determined by liquid scintillation counting after separation of the compounds by column chromatography. The experimental conditions ensured a minor contribution of 3H-metabolites to the evoked total tritium overflow.
The release of 3H-noradrenaline evoked by nerve stimulation or high K+ solution was decreased in the presence of the muscarinic agonist, methacholine. N-methylatropine reversed the inhibition completely. Thus, the rat heart contains inhibitory muscarine receptors modulating noradrenaline release from adrenergic nerve fibres.
In order to compare the presynaptic muscarine receptors with postsynaptic muscarine receptors in one and the same organ, the pA2 values of N-methylatropine and pirenzepine at both of these sites were measured. The antagonism of methacholine-induced inhibition of 3H-noradrenaline over-flow was determined as the presynaptic parameter. pA2 values of 9.61 for N-methylatropine and 6.63 for pirenzepine were found. The methacholine-induced inhibition of the atrial tension development of isolated left rat atria paced at 2 Hz was measured as a postsynaptic parameter. pA2 values of 9.90 for N-methylatropine and 6.69 for pirenzepine were found.
The postsynaptic pA2 values did not differ from the presynaptic affinity constants indicating that neither substance revealed differences in structure between neuronal and myocardial muscarine receptors in the rat heart.
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Abbreviations
- DOMA:
-
3,4-dihydroxymandelic acid
- DOPEG:
-
3,4-dihydroxyphenylglycol
- MCh:
-
methacholine
- MOPEG:
-
3-methoxy-4-hydroxyphenylglycol
- NA:
-
noradrenaline
- NMN:
-
normetanephrine
- OMDA:
-
O-methylated deaminated metabolites (sum of MOPEG and VMA)
- VMA:
-
3-methoxy-4-hydroxymandelic acid
References
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58
Birdsall NJM, Hulme EC (1979) Biochemical studies on muscarinic acetylcholine receptors. J Neurochem 27:7–16
Birdsall NJM, Burgen ASV, Hammer R, Hulme EC, Stockton J (1980) Pirenzepine — a ligand with original binding properties to muscarinic receptors. Scand J Gastroenterol 15 (Suppl) 66:1–4
Brown DA, Fatherazi S, Garthwaite J, White RD (1980a) Muscarinic receptors in rat sympathetic ganglia. Br J Pharmacol 70:577–592
Brown DA, Forward A, Marsh S (1980b) Antagonist discrimination between ganglionic and ileal muscarinic receptors. Br J Pharmacol 71:362–364
Carpenter JR, Nash CW (1976) Release of [3H]noradrenaline from perfused rat hearts by potassium and its modifications by 6-hydroxydopamine and reserpine. Can J Physiol Pharmacol 54:907–915
Documenta Geigy Wissenschaftliche Tabellen (1973) K Diem and C Lentner (eds) 7th ed. equation (672). Ciba Geigy Ltd., Basel, p 178
Fozard JR, Muscholl E (1972) Effects of several muscarinic agonists on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart. Br J Pharmacol 45: 616–629
Fuder H (1982) The affinity of pirenzepine and other antimuscarinic compounds for pre- and postsynaptic muscarine receptors of the isolated rabbit and rat heart. Scand J Gastroenterol (Suppl) (in press)
Fuder H, Muscholl E, Wegwart R (1976) The effects of methacholine and calcium deprivation on the release of the false transmitter, α-methyladrenaline, from the isolated rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 293:225–234
Fuder H, Meiser C, Wormstall H, Muscholl E (1981a) The effects of several muscarinic antagonists on pre- and postsynaptic receptors in the isolated rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 316:31–37
Fuder H, Rink D, Alt B (1981b) Pirenzepine (Pi) and functional pre- and postsynaptic muscarine receptors in rat and rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 316:R52
Graefe KH, Stefano FJE, Langer SZ (1973) Preferential metabolism of (-)-[3H]norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160
Halim S, Kilbinger H, Wessler I (1982) Pirenzepine does not discriminate between pre- and postsynaptic muscarine receptors on the guineapig small intestine. Scand J Gastroenterol (Suppl) (in press)
Hammer R, Berrie CP, Birdsall NJM, Burgen ASV, Hulme EC (1980) Pirenzepine dist nguishes between different subclasses of muscarinic receptors. Nature 283:90–92
Huković S, Muscholl E (1962) Die Noradrenalin-Abgabe aus dem isolierten Kaninchenherzen bei sympathischer Nervenreizung und ihre pharmakologische Beeinflussung. Naunyn-Schmiedebergs Arch Exp Pathol Pharmakol 244:81–96
Khan MT, Malik KU (1980) Inhibitory effect of adenosine and adenine nucleotides on potassium-evoked efflux of [3H]-noradrenaline from the rat isolated heart: lack of relationship to prostaglandins. Br J Pharmacol 68:551–561
Muscholl E (1980) Peripheral muscarinic control of norepinephrine release in the cardiovascular system. Am J Physiol 239:H713-H720
Muscholl E (1982) Cholinergic-adrenergic interactions at the presynaptic levels as studied in the heart. In: Proc 8th Intern Congress of Pharmacology, Tokyo, July 1981, Neurotransmitters — Receptors, vol 2. Pergamon Press, Oxford (in press)
Roffler Tarlov S, Langer SZ (1971) The fate of 3H-norepinephrine released from isolated atria and vas deferens: effect of field stimulation. J Pharmacol Exp Ther 179:186–197
Sachs L (1974) Angewandte Statistik, 4. Aufl. Springer, Berlin Heidelberg New York, pp 339–340
Sharma VK, Banerjee SP (1978) Presynaptic muscarinic cholinergic receptors. Nature 272:276–278
Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124
Starke K, Hedler L (1981) Dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA) as metabolites of endogenous and exogenous noradrenaline (NA). Naunyn-Schmiedeberg's Arch Pharmacol 316:R55
Starke K, Steppeler A, Zumstein A, Henseling M, Trendelenburg U (1980) False labelling of commercially available 3H-catecholamines? Naunyn-Schmiedeberg's Arch Pharmacol 311:109–112
Story DD, Briley MS, Langer SZ (1979) The effects of chemical sympathectomy with 6-hydroxydopamine on α-adrenoceptor and muscarinic cholinoceptor binding in rat heart ventricle. Eur J Pharmacol 57:423–426
Wallenstein S, Zucker LC, Fleiss JL (1980) Some statistical methods useful in circulation research. Circ Res 47:1–9
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Fuder, H., Rink, D. & Muscholl, E. Sympathetic nerve stimulation on the perfused rat heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 210–219 (1982). https://doi.org/10.1007/BF00500482
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DOI: https://doi.org/10.1007/BF00500482