Evidence for M1 muscarinic cholinoceptors mediating facilitation of noradrenaline release in guinea-pig carotid artery.
The muscarinic agonists acetylcholine (1-50 mumol/l), carbachol (1-10 mumol/l) and McN-A-343 (1-50 mumol/l, selective for M1 receptors) increased, in a concentration-dependent manner, the electrically-evoked tritium overflow from guinea-pig carotid arteries preincubated with [3H]-noradrenaline. The increase caused by acetylcholine was not modified by hexamethonium (300 mumol/l) but was reduced by the muscarinic receptor antagonists methylatropinium (0.5 and 1 nmol/l, non-selective), pirenzepine (1 and 5 nmol/l, M1-selective), methoctramine (1 and 5 mumol/l, M2-selective) and p-fluoro-hexahydro-sila-difenidol (0.1-1 mumol/l, M3-selective). The order of potencies (expressed as negative logarithms of concentrations that reduced by 50% the facilitatory effect of acetylcholine) was: methyl-atropinium (9.93) > pirenzepine (8.83) > p-fluoro-hexahydro-siladifenidol (6.81) > or = methoctramine (6.20). These results demonstrate the existence of facilitatory M1 receptors modulating noradrenaline release in blood vessels.
Casado
M A
MA
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Marín
J
J
Salaices
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D006168:Guinea Pigs; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D000109:Acetylcholine; D009638:Norepinephrine