caa a22 4500 469079045 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF00164574 doi (NATIONALLICENCE)springer-10.1007/BF00164574 Presynaptic muscarinic receptor subtypes involved in the inhibition of acetylcholine and noradrenaline release in bovine cerebral arteries [Elektronische Daten] [M. Ferrer, R. Galvín, J. Marín, G. Balfagón] Summary: Experiments were performed in bovine cerebral arteries preincubated with [3H]-choline or [3H]-noradrenaline to analyze the presynaptic muscarinic receptors involved in inhibition of acetylcholine and noradrenaline release induced by electrical stimulation (4 Hz, 200 mA, 0.3 ms, 1 min). For this purpose, the actions of several muscarinic receptor antagonists on the 3H overflow and on the carbacol-induced inhibition of this overflow were assessed. The evoked [3H]-acetylcholine release and [3H]-noradrenaline release were markedly reduced by the presence of tetrodotoxin, Ca2+-free medium, and the inhibitor of both choline transport and choline acetyltransferase, AF64A. Chemical sympathetic denervation with 6-hydroxydopamine (6-OHDA) decreased the uptake of[3H]-noradrenaline, and AF64A reduced mainly the uptake of [3H]-choline, but also of [3H]-noradrenaline. Carbachol reduced the evoked [3H]-noradrenaline and [3H]-acetylcholine release; the IC50 values were 0.37 and 0.43 μmol/l, respectively. Atropine and 4-DAMP, but not AF DX 116, methoctramine or pirenzepine, increased the evoked [3H]-acetylcholine release. However, these muscarinic antagonists failed to modify the evoked [3H]-noradrenaline release. Carbachol inhibited the release of both acetylcholine and noradrenaline. The inhibition was blocked by the antagonists. The rank orders of potency (based on plC50 values) were, in the case of [3H]-acetylcholine release, atropine > 4-DAMP >AF-DX 116 >- pirenzepine >- methoctramine, and, in the case of [3H]-noradrenaline release, atropine > 4-DAMP > AF-DX 116 >- methoctramine >-pirenzepine. These results suggest (1) that the prosynaptic receptors that modulate endogenous acetylcholine release are likely of the M3 subtype, whilst those involved on the effect of the exogenous agonist Carbachol are of M2 subtype, and (2) that those which inhibit noradrenaline release are probably a mixture of M2 and M3 subtypes as well. The autoinhibition of the acetylcholine release was funtionally active under our experimental conditions, while noradrenaline release does not appear to be modulated by muscarinic receptors in physiological conditions. Springer-Verlag, 1992 Bovine cerebral arteries nationallicence Presynaptic receptors nationallicence Muscarinic receptors nationallicence Acetylcholine release nationallicence Noradrenaline release nationallicence Ferrer M. Departamento de Fisiología, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut Galvín R. Departamento de Fisiología, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut Marín J. Departamento de Farmacología y Terapeútica, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut Balfagón G. Departamento de Fisiología, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 619-626 0028-1298 345:6<619 1992 345 210 https://doi.org/10.1007/BF00164574 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00164574 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ferrer M. Departamento de Fisiología, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut NATIONALLICENCE 700 1- Galvín R. Departamento de Fisiología, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut NATIONALLICENCE 700 1- Marín J. Departamento de Farmacología y Terapeútica, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut NATIONALLICENCE 700 1- Balfagón G. Departamento de Fisiología, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, E-28029, Madrid, Spain aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 619-626 0028-1298 345:6<619 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer